© 2009 Joseph J Collins, RN, ND1 By: Joseph J Collins, RN, ND Naturopathic Consultant Presented at: 17 th ANNUAL WORLD CONGRESS ON ANTI-AGING MEDICINE

© 2009 Joseph J Collins, RN, ND 1

By:

Joseph J Collins, RN, NDNaturopathic Consultant

Presented at:

17th ANNUAL WORLD CONGRESS ON ANTI-AGING MEDICINE

& REGENERTIVE BIOMEDICAL TECHNOLOGIES

Las Vegas, Nevada, USADec. 9 – 12, 2009

Main Stage, Saturday 9:30 a.m.

. Thought for the day:

All inflammation is systemic inflammation.

Systemic Enzyme Therapy:Anti-Inflammatory & Anti-Aging

Applications

www.SystemicEnzymeSupport.org

http://www.systemicenzymesupport.org/

Objectives, Disclaimer, Copyright & PermissionsObjectives, Disclaimer, Copyright & Permissions


1. Review biomarkers of inflammation that have systemic affects on diverse body systems.

2. Review mediators of inflammation.3. Understand the mechanisms of action by which systemic

enzyme therapy with Wobenzym® decreases mediators of inflammation.

4. Understand clinical applications for systemic enzyme therapy with Wobenzym® as they relate to degenerative diseases and progression of senescence.

References: Each slide has its own numbered references in the Notes Page view of the presentation.


Disclaimers: This presentation is for Educational Purposes Only. The entire contents of this presentation, are for informational purposes only. The contents are not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in this presentation. These statements made in this presentation have not been evaluated by the Food and Drug Administration and are not intended to be used to diagnose, treat, cure or prevent any diseases. The Content is the opinion of the author, and does not represent the opinion of any other party.

Copyright & Permissions: This entire presentation and all images herein are copyright of Joseph J Collins and SystemicEnzymeSupport.org. This presentation may be used for scientific, clinical and patient education in its entirety without editing or modification.


What is Systemic Enzyme Therapy?What is Systemic Enzyme Therapy?


Systemic Enzyme Therapy (also called Systemic Enzyme Support) is a treatment modality that uses Wobenzym® formulations to increase serum levels of proteolytic enzymes, which in turn activate α-2-macroglobulin - a serum protein that facilitates the binding and removal of foreign peptides, excessive inflammatory mediators and auto-toxic endogenous proteins - and thereby support balanced humoral immune function and modulate systemic inflammation.



BIOMARKERS OF INFLAMMATIONBIOMARKERS OF INFLAMMATION


• Increased Erythrocyte Sedimentation Rate

• Increased C-Reactive Protein

• Abnormal Immunoglobulins Levels (IgG, IgE, IgA, IgM)

• Increases Circulating Immune Complexes

• Increase Cytokine Production with an Imbalance of Cytokines

• Increased Fibrin Activation & Fibrosis [(Prothrombin Time (PT)]

• Increased Amyloid Production & Deposition

Other Mediator of inflammation:

• Damaged Proteins and Cellular Debris (glycosylated, oxidized , and other auto-toxic endogenous proteins)



Erythrocyte Sedimentation RateErythrocyte Sedimentation Rate


ESR:In RA patients free of overt arterial disease, there is a direct relationship between cumulative inflammatory burden (ESR area-under-the-curve-years) & arterial stiffness.[1]

Systemic Enzyme Therapy:Erythrocyte Sedimentation Rate (ESR) is lowered in RA patients treated with Wobenzym® N and Wobenzym® PS.[2,3,4]

Wobenzym® formulations lowered ESR levels in relapsing urinary tract infections, adnexitis , and acute trauma.[5,6,7]

[Shaivok A.V.,1997], [Pavelka-Study No.: MU-693405] www.SystemicEnzymeSupport.org


C-Reactive ProteinC-Reactive Protein


C-Reactive ProteinElevated CRP levels are a marker of systemic inflammation that

is associated with not only cardiovascular disease, but also dementia, pulmonary disease and lymphatic dysfunction.[1,2,3]

Systemic Enzyme Therapy:In lymphedema patients on Wobenzym®, there was a mean

percent change of CRP from baseline of –39.8% compared to –17.4% in the placebo group.[3]

Wobenzym® also lowered CRP levels in rheumatoid arthritis and acute trauma.[4,5]



Abnormal Immunoglobulins LevelsAbnormal Immunoglobulins Levels


Abnormal Immunoglobulins Levels

Elevated Immunoglobulins occur in neuro-degenerative diseases such as Alzheimer’s (high Iga), as well as atopic dermatitis, recurrent infections, & rheumatoid arthritis.[1,2,3,4]

Systemic Enzyme Therapy:Wobenzym® PS therapy resulted in normalization of IgA in 60 %

of recurrent infection patients and reduction of primarily elevated IgE levels in 93 % of patients. [3]

Wobenzym® lowers autoimmune antibodies in autoimmune diseases such as rheumatoid arthritis and eczema. [2,4]



Circulating Immune ComplexesCirculating Immune Complexes


Circulating Immune Complexes

Elevated CIC are contributory to the progression of liver disease, atherosclerosis, complications for diabetes, myocardial re-infarction, atopic dermatitis, rheumatoid arthritis, Behcet's disease, and other immune complex diseases.[1,2,3,4,5,6,7,8,9]

Systemic Enzyme Therapy:Wobenzym® decreased CIC levels an additional 45% when

used as an adjuvant (with methotrexate) in rheumatoid arthritis.[8]

Wobenzym® lowered CIC levels in patients with liver disease, diabetes, myocardial infarction, atopic dermatitis & Behcet's disease.[1,2,3,4,5,6,7,9]



Imbalance of CytokinesImbalance of Cytokines


Imbalance of CytokinesIncreased pro-inflammatory cytokines (Th1) contribute to the

progression degenerative diseases such as rheumatoid arthritis, while excessive TGF-beta (a Th2 cytokine) is seen in many inflammatory disorders (pulmonary fibrosis, cataracts, & certain cancers).[1,2,3]

Systemic Enzyme Therapy:In clinical studies, Wobenzym® therapy decreased excessive

pro-inflammatory cytokines (IL-1b and TNF-alpha in RA patients, while in other studies it decreased excessive TGF-beta.[4]



Increased Fibrin Activation & FibrosisIncreased Fibrin Activation & Fibrosis


Increased Fibrin Activation & Fibrosis

Increased fibrin activation and/or fibrosis is found in a number of acute & degenerative conditions including phlebitis, rheumatoid arthritis and some cancers.[1,2,3]

Systemic Enzyme Therapy:In postphlebitic syndrome, the effect of Wobenzym® PS therapy

was more pronounced (84% vs 73% for conventional therapy) due to increased blood fibrinolytic activity and inhibited platelet function.[1]

Both increased blood fibrinolytic activity and increased proteolysis of extravascularly deposited fibrin are observed in a number of clinical conditions treated with Wobenzym® .[1,2,3,4,5,6,7,8]



Increased Amyloid Production & DepositionIncreased Amyloid Production & Deposition


Increased Amyloid Production & DepositionAccumulation of beta-amyloid peptide in the brain plays a

central role in the development and progression of Alzheimer’s disease (AD).[1,2,3]

Systemic Enzyme Therapy:Wobenzym® activates alpha-2-macroglobulin and its receptor,

low density lipoprotein receptor-related protein (LRP), which function together to facilitate the cellular uptake and degradation of -amyloid peptide. [1,2,3]



Damaged Proteins and Cellular Debris Damaged Proteins and Cellular Debris


Damaged Proteins and Cellular Debris The formation of toxic protein aggregates is a common denominator to many neurodegenerative diseases and aging. Accumulation of toxic, possibly infectious protein aggregates induces a cascade of events, such as excessive inflammation, the production of reactive oxygen species, apoptosis and neuronal loss.[1]

Systemic Enzyme Therapy:Wobenzym® activation of α2M modulates a potent chaperone-like action of α2M that has broad specificity for proteins partly unfolded as a result of heat or oxidative stress. α2M patrols extracellular spaces for unfolded/misfolded proteins and facilitate their disposal.[1,2]



Mediators of InflammationMediators of Inflammation


EXOGENOUS MEDIATORS OF INFLAMMATION

Bacterial, viral, parasitic, fungaland mycobacterial pathogens and the toxins they produce.

ENDOGENOUS MEDIATORS OF INFLAMMATION

ANTIBODIES

CIRCULATING IMMUNE COMPLEXES

CYTOKINES

Fibrin Amyloid CRP Protein Debris


Systemic Enzyme FormulationSystemic Enzyme Formulation

© 2009 Joseph J Collins, RN, ND 14www.SystemicEnzymeSupport.org

trans-mucosal Absorption trans-mucosal Absorption


Wobenzym® PS is delivered through tablets which have a special enteric coating that can withstand the acid environment in the stomach (very important since enzymes can be damaged by stomach acid). Once the tablet has passed a safe distance from the stomach acids, the tablet dissolves and the enzymes are efficiently absorbed by the mucosal membrane of the intestine. This process is most effective if the tablets are taken away from meals (45 minutes before meals or 1 ½ hour after meals).[1]


α-2M Activationα-2M Activation


After being absorbed, the proteolytic enzymes tryspin and bromelain, from Wobenzym® PS, will preferentially complex to the bait region of alpha-2-macroglobulin (a2M)) to create α-2-macroglobulin-protease complexes.[1,2]

a2M, a high molecular weight plasma glycoprotein (8-10 % of total serum protein) that functions as a binding, carrier, and targeting protein. It binds host or foreign peptides and particles, thereby serving as humoral defense barriers against pathogens in both the plasma and the tissue.[3]


Binding the Mediators of InflammationBinding the Mediators of Inflammation


This trapping of 2 protease molecules from Wobenzym® into the a2m changes the configuration of α-2-macroglobulin so that the newly activated α-2-macroglobulin-protease complex now has increased capacity for binding excessive interstitial and intravascular cytokines, immunoglobulins, fibrin, CRP, amyloid beta proteins, cell debris, and proteins damaged by oxidative stress and glycosylation.[1,2,3,4,5,6,7,8,9,10,11]


Clearance of α-2M-Protease-MI Complexes Clearance of α-2M-Protease-MI Complexes


Wobenzym® PS increases alpha-2-macroglobulin-proteinase complexes, which are activated for receptor mediated endocytosis and are readily removed by hepatic α-2M-receptors (α-2M-R), as well as other cells expressing α-2M-R, such as macrophages. [1]

The alpha 2-macroglobulin-proteinase complexes promote macrophage locomotion and chemotaxis, such that the activated alpha 2-macroglobulin-proteinase complexes and the inflammatory mediators bound to the complex are cleared from the circulation very quickly by macrophages. [2,3]


RESTORATION OF HEALTHY BIOMARKERSRESTORATION OF HEALTHY BIOMARKERS


Based on clinical studies, use of Wobenzym® results in the following changes in mediators of inflammation:

Decreased Erythrocyte Sedimentation Rate[1,2,3,4,5,6]

Decreased C-Reactive Protein Levels [7,8,9]

Decreased Circulating Immune Complex Levels [10,11,12,13,14,15,16,17,18,19]

Normalization of Cytokine Levels [21,21,22,23]

Normalization of Immunoglobulins (IgG, IgE, IgA, IgM) [24,25,26]

Restore Normal Fibrinolytic Activity [27,28]

Increased Amyloid Catabolism [29,30,31,32,33,34]


Clinical ApplicationsClinical Applications


Wobenzym® formulations are clinically effective in a broad range of degenerative conditions due to its immunomodulatory, anti-inflammatory, anti-edema, analgesic, fibrinolytic, thrombolysis, anti-tumor and antioxidant properties. Dozens of randomized, blinded and placebo studies have evidenced that the specific formulation can be used in various clinical specialties, including the following:

Andrology, Men’s HealthArthritis, Rheumatology Osteoarthritis Rheumatoid Diseases Reactive arthritis FibromylagiasCardiologyDentistry DiabetologyHepatology

Immunology/Infectious DiseasesLymphologyNephrologyNeurologyOncologyOtolaryngologyPulmonologyTraumatology, SurgeryUrologyVascular Medicine


Learn More About Wobenzym®Learn More About Wobenzym®

Professional Postersdigital copies of posters are on-line

www.SystemicEnzymeSupport.org• Tutorial on Systemic Enzyme Support• Conditions Treated with Systemic Enzymes• Clinical Research Summaries and Abstracts• Professional Articles (Technical)• Dosage Guidelines • Presentations• Contact Info

This presentation (references in note section) is available at: www.SystemicEnzymeSupport.org/presentations/


Documents

© 2009 Joseph J Collins, RN, ND1 By: Joseph J Collins, RN, ND Naturopathic Consultant Presented at: 17 th ANNUAL WORLD CONGRESS ON ANTI-AGING MEDICINE