matrix is mainly made of polysaccharides and proteins providing structural stability and protection to the microbes.

Within biofilms, the microbes can replicate, share nutrients, and exchange genomic information (i.e. antibiotic resistance genes), making biofilms a sociomicrobiological “paradise” for microbes to thrive. [2]

Infectious microbes commonly known to produce biofilms include Staphylococcus sp., Pseudomonas aeruginosa, Streptococcus sp., Listeria monocytogens, Clostridium sp., N. gonorrhea, and Candida albicans.

Development of a biofilm starts with planktonic (free-moving) bacteria reversibly attaching to a surface [Figure 1]. Bacteria will then irreversibly bind to the surface within the next few hours or days while they replicate and begin to produce a polymer matrix to surround the microcolonies - forming biofilm. The biofilm can continue to grow and eventually possess tolerance to antibiotics, as well as chemical disinfectants.

Evidence has shown that the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of antibiotics to biofilm-growing bacteria may be up to 100-1000 times higher compared with free-moving bacteria. [3],[4],[5]

Biofilms can also help bacteria grow in vitro on abiotic surfaces, making biofilm-growing bacteria a serious

BiofilmXBiofilm Disrupting Formula VA-139

Key Features:BiofilmX combines multiple fibrinolytic & mucolytic enzymes to help breakdown biofilms and augment the efficacy of anti-microbial agents when taken together.

• Serrapeptase - a potent mucolytic enzyme that help reduce the inhibitory effects of bacterial biofilms, enhance anti-microbial effect, and decrease chronic inflammation.

• Systemic fibrinolytic proteases and polysaccharide-digesting enzymes to help breakdown the integrity of biofilms and their adhesion to target tissues.

• Alpha lipoic acid - a sulfurhydryl-containing compound known to disrupt biofilm formation and provide antioxidant protection to the host.

• Enteric-release encapsulation (FREE of phthalates that are commonly found in enteric coating) to bypass stomach acid.

Clinical Applications:• Decrease inflammatory edema.• Accelerates the elimination of sputum, pus and hematoma.

• Enhance pathogen eradication of antibiotics/ antimicrobials.

Description: Antibiotic resistance has become increasingly prevalent in the past decade, and is now a global pandemic. Each year in the United States, more than 2,000,000 people acquire serious infections with bacteria that are resistant to one or more of the antibiotics designed to treat those infections. At least 23,000 people die each year as a direct result of these antibiotic-resistant infections, and many more die from other conditions that were complicated by an antibiotic-resistant infection.[1]

The mechanisms of antibiotic-resistance include gene mutation, plasmid transfer, depletion of beneficial bacteria by antibiotics, allowing drug-resistant bacteria to take over, and BIOFILM formation, which is one of the most important mechanisms for chronic infectious diseases.

What are Biofilms?Biofilms are a biopolymer matrix produced by microbes. The

Quantity: 84 Vegetarian Capsules Ingredients (per capsule): Serrapeptase (from Serratia marcescens E-15)...........30,000 SUProtease (from Aspergillus oryzae)............................15,000 HUTAlkaline Protease (*Nattozimes®)...............4,225 HUT (1,500 FU) (from Aspergillus oryzae & Aspergillus melleus)Xylanase (from Trichoderma longibrachiatum)...............1,100 XUPectinase (from Aspergillus niger)................................50 endo-PBeta-Glucanase (from Trichoderma longibrachiatum)......30 BGUGlucoamylase (from Aspergillus niger).............................25 AGUHemicellulase (from Aspergillus niger)....................... 4,000 HCUCellulase (from Aspergillus niger).....................................500 CUAlpha Lipoic Acid...............................................................200 mg

*Nattozimes® is a registered trademark of National Enzyme Company®

Non-medicinal Ingredients: Silicon dioxide, L-Leucine, pullulan/ hypromellose (capsule)

Suggested Use: Adults - Take 1 capsule with meal, 3 times a day, or as directed by a health care practitioner. Consult a health care practitioner for use beyond 4 months.

814741

00139

0

Enteric Release (Free of Pthalate)Biofilm Disrupting FormulaWith proteolytic & mucolytic enzymes to help break down mucous

Sortie Entérique (Sans Pthalate)Formule perturbatrice de BiofilmAvec des enzymes protéolytique et mucolytiques pour aider à dissoudre le mucus

Ingr

edie

nts/

Ingr

édie

nts (

per/

par

cap

sule

):Se

rrap

epta

se (f

rom

/de

Serr

atia

mar

cesc

ens E

-15)

......

......

......

....3

0,00

0 SU

Prot

ease

(fro

m/d

e As

perg

illus

ory

zae)

......

......

......

......

......

......

..15,

000

HUT

Alka

line

Prot

ease

(Na�

ozim

es®)

......

......

......

......

......

..1,5

00 F

U (4

,225

HU

T)

(from

/de

Aspe

rgill

us m

elle

us &

Asp

ergi

llus o

ryza

e)Xy

lana

se (f

rom

/de

Tric

hode

rma

long

ibra

chia

tum

).....

......

......

......

1,10

0 XU

Pec�

nase

(fro

m/d

e As

perg

illus

nig

er)..

......

......

......

......

......

......

...50

End

o-P

Beta

-Glu

cana

se (f

rom

/de

Tric

hode

rma

long

ibra

chia

tum

).....

......

....3

0 BG

UGl

ucoa

myl

ase

(from

/de

Aspe

rgill

us n

iger

).....

......

......

......

......

......

....2

5 AG

UHe

mic

ellu

lase

(fro

m/d

e As

perg

illus

nig

er)..

......

......

......

......

......

..4,0

00 H

CUCe

llula

se (f

rom

/de

Aspe

rgill

us n

iger

).....

......

......

......

......

......

......

......

500

CUAl

pha

Lipo

ic A

cid/

Aci

de a

lpha

-lipo

ïque

......

......

......

......

......

......

......

.200

mg

*Na�

ozim

es®

is a

regi

ster

ed tr

adem

ark

of N

a�on

al E

nzym

e Co

mpa

ny®/

N

a�oz

imes

® es

t une

mar

que

dépo

sée

de N

a�on

al E

nzym

e Co

mpa

ny®

Non

-med

icin

al In

gred

ient

s/ In

gréd

ient

s Non

-méd

icin

aux:

Si

licon

dio

xide

/ dio

xyde

de

silic

ium

, L-le

ucin

e, h

ypro

mel

lose

(cap

sule

)Su

gges

ted

Use

/ U

�lis

a�on

Sug

géré

e:

Adul

ts –

Tak

e 1

caps

ule,

3 �

mes

a d

ay, o

r as

dire

cted

by

a he

alth

care

pr

ac��

oner

. Con

sult

a he

alth

car

e pr

ac��

oner

for u

se b

eyon

d 4

wee

ks./

Ad

ulte

s -

Pren

dre

1 ca

psul

e, 3

fois

par

jour

, ou

selo

n le

s in

dica

�ons

de

votr

e pr

a�ci

en d

e so

ins d

e sa

nté.

Con

sulte

r un

pra�

cien

de

soin

s de

sant

é si

l'usa

ge se

pro

long

e au

-del

à de

4 se

mai

nes .

Cau�

on/

Mis

e en

Gar

de:

Do n

ot u

se if

you

are

pre

gnan

t or b

reas

�eed

ing.

Alle

rgy

has

been

kno

wn

to o

ccur

; in

whi

ch ca

se, d

iscon

�nue

use

. Con

sult

a he

alth

care

pra

c��o

ner

prio

r to

use

if

you

have

a g

astr

oint

es�n

al l

esio

n/ul

cer,

are

taki

ng

an�c

oagu

lant

or a

n�-in

flam

mat

ory

med

ica�

on, o

r are

hav

ing

surg

ery;

or

if yo

u ha

ve

diab

etes

. Di

scon

�nue

us

e an

d co

nsul

t a

heal

thca

re

prac

��on

er i

f yo

u ex

perie

nce

swea

�ng,

pal

enes

s, c

hills

, he

adac

he,

dizz

ines

s and

/or c

onfu

sion

(ie. s

ympt

oms o

f low

blo

od su

gar)

./

Ne

pas

u�lis

er s

i vou

s êt

es e

ncei

nte

ou s

i vou

s al

laite

z. H

yper

sens

ibili

té,

telle

une

alle

rgie

, peu

t se

man

ifest

er. S

i tel

est

le c

as, c

esse

r l'u

�lisa

�on.

Co

nsul

ter

un p

ra�c

ien

de s

oins

de

sant

é av

ant

d'en

faire

l'us

age

si vo

us

avez

de

s lé

sions

ga

stro

-inte

s�na

les/

ulcè

res,

si

vous

pr

enez

de

s an

�coa

gula

nts

ou d

es a

n�-in

flam

mat

oire

, ou

si

vous

dev

ez s

ubir

une

chiru

rgie

; ou

si vo

us a

vez

le d

iabè

te. S

i vou

s dé

velo

ppez

des

sym

ptôm

es

tels

que

de la

tran

spira

�on,

de

la p

âleu

r, de

s fr

isson

s, d

es m

aux

de tê

te,

des

étou

rdiss

emen

ts

et/o

u de

la

co

nfus

ion,

ce

sser

l'u

�lisa

�on

et

cons

ulte

r un

pra�

cien

de

soin

s de

sant

é (c

ar c

es sy

mpt

ômes

peu

vent

êtr

e ca

usés

par

un

faib

le ta

ux d

e su

cre

dans

le sa

ng).

Stor

e at

ro

om

tem

pera

ture

aw

ay

from

he

at

and

moi

stur

e (<

30o C/

<60%

RH).

Plea

se fi

nish

con

sum

ing

the

prod

uct

with

in 6

0 da

ys

a�er

ope

ning

. Do

not

use

if c

ap s

eal i

s br

oken

. Ke

ep o

ut o

f re

ach

of

child

ren.

/ Co

nser

ver

à la

tem

péra

ture

am

bian

te lo

in d

e la

cha

leur

et d

e l’h

umid

ité

(<30

o C/<6

0%RH

). S’

il vo

us

plaî

t te

rmin

er

le

prod

uit

est

cons

omm

é da

ns le

s 60

jour

s apr

ès o

uver

ture

. Ne

pas u

�lise

r si l

e sc

eau

de

sécu

rité

est b

risé

ou m

anqu

ant.

Gard

ez h

ors d

e po

rtée

des

enf

ants

.

Man

ufac

ture

d by

/ Fab

riqué

par

: Nat

uro

Aid

Phar

mac

eu�c

al In

c.M

aple

Rid

ge, B

.C.,

V2X

8G1,

Can

ada

| w

ww

.vita

aid.

com

84 Vegetarian Capsules NPN 80078777

BiofilmX

Vegan

Form

ulas

Form

ules

Veg

an

Figure 1. Development of Biofilms [Source: https://microbewiki.kenyon.edu/index.php/Biofilms_and_Human_Implants]

potential hazard in the food industry (eg. Listeria) and hospital /surgical settings (eg. MRSA).[6]

Illnesses caused by biofilm-forming microbes include:• Chronic sinusitis and UTI’s• S. aureus skin infection• Antibiotic-associated enteritis caused by Clostridiumdifficile• Candidiasis • Autistic behaviors caused by neurotoxins from Clostridium

overgrowth• Lyme disease

Fibrin & BiofilmsFibrin is an important part of our body’s defense mechanism to protect tissues from infections and the inflammatory response caused by pathogens. However, many types of bacteria have evolved to exploit this mechanism to their own benefits.

To these bacteria, fibrin is like an adhesive matrix.[8] These molecules help bacteria establish and colonize more easily on plasma-coated surfaces of the host where fibrin/fibrinogen molecules are abundant.

Moreover, many bacteria, such as Staphylococcal sp., are able to secrete the enzyme - coagulase - to thicken blood by converting fibrinogen to fibrin; they then deposit the fibrin on their own surfaces to form scaffolds of biofilms and shield against opsonophagocytosis (ie. antibody-mediated phagocytosis).[5] Such a protective mechanism can even extend to other microbes co-infecting the area, such as Candida albicans.[9]

“Fibrinolytic Proteases” Disrupt BiofilmsEnzymes that possess both fibrinolytic and proteolytic activities may play a pivotal role in enhancing the effectiveness of antimicrobials because they are not only able to disperse the biofilms but also break the adhesion of biofilms to targeted tissues. Evidence has shown that breaking the integrity of biofilms not only allows more antimicrobial molecules to enter the infected tissue, but also exposes the microbes to the body’s immune system.

Serrapeptase and Nattozimes® are both potent systemic proteases that can help break down the biofilms of bacteria, such as S. aureus and Listeria, [11] attenuating their invasion abilities.

Serrapeptase is commonly used to alleviate post-operation swelling and pain due in parts to its anti-inflammatory & anti-edemic effects.[12] It’s also demonstrated beneficial effects in people with chronic airway disease [13] and acute/chronic ear-nose-throat inflammations.[14]

In Japan, serrapeptase is a widely used ‘pharmaceutical’ adjunctive medicine to various antibiotics to treat and prevent implant-related infections.[15],[16]

Polysaccharide-Digesting EnzymesDue to the fact that biofilms are also consisted of various sugar polymers, polysaccharide-digesting enzymes have been shown to help break down bacterial biofilms and enhance the

effectiveness of antiseptic agents.[17],[18] BiofilmX includes various polysaccharidases, especially ones not produced by the body, to combat a wider spectrum of microbial biofilms internally.

Mucolytic Thiol Group in Alpha Lipoic Acid (ALA)Thiol - or sulphhydryl group (R-SH) - is known to exert mucolytic effect. The most well-known mucolytic thiol-agent is N-acetylcysteine (NAC), which has only one R-SH group. While it has demonstrated its ability to help anbiotics like penicllins break biofilm to increase their efficacy, NAC has also been shown to reduce the effectiveness of antibiotics, such as aminocyclitols. [19]

ALA, in its reduced form, has 2 sulphhydryl groups to provide comparable if not greater anti-biofilm benefits [20], and without being shown to reduce the efficacy of any antibiotics.

Reference: 1. Centers for Disease Control and Prevention. U.S. Department of Health and Human

Services. 2013.2. Costerton W, Veeh R, Shirtliff M, Pasmore M, Post C, Ehrlich G. The application of

biofilm science to the study and control of chronic bacterial infections. J Clin Invest 2003;112:1466-77.

3. Anwar H, Costerton JW. Enhanced activity of combination of tobramycin and piperacillin for eradication of sessile biofilm cells of Pseudomonas aeruginosa. Antimicrob Agents Chemother 1990;34:1666-71.

4. Moskowitz SM, Foster JM, Emerson J, Burns JL. Clinically feasible biofilm susceptibility assay for isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. J Clin Microbiol 2004;42:1915-22.

5. Bjarnsholt T, Kirketerp-Muller K, Kristiansen S, Phipps R, Nielsen AK, Jensen PØ, et al. Silver against Pseudomonas aeruginosa biofilms. APMIS 2007;115:921-8.

6. Hoiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. IJAA 2010; 35(4): 322-332.

7. Johnson LL, Berggren KN, Szaba FM, Chen WX, Smiley ST. Fibrin-mediated protection against infection-stimulated immunopathology. J Exp Med. 2003; 197(6): 801-806.

8. Foster TJ, Geoghegan JA, Ganesh VK, Hook M. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat Rev Microbiol 2014; 12:49-62.

9. Fehrmann C, Jurk K, Bertling A, Seidel G, Fegeler W, Kehrel BE, Peters G, Becker K, Heilmann C. Intrn J Med Microbio (2013); 303:230-238.

10. Zapotoczna M, McCarthy H, Rudkin JK, O’Gara JP, O’Neill E. An essential role for coagulase in Staphylococcus aureus biofilm development reveals new therapeutic possibilities for device-related infections. JID 2015; 212: 1883-1893.

11. Longhi C, Scoarughi GL, Poggiali F, Cellini A, Carpentieri A, Seganti L, Pucci P, Amoresano A, Cocconcelli PS, Artini M, Costerton JW, Selan L. Protease treatment affects both invasion ability and biofilm formation in Listeria monocytogenes. Microb Pathog. 2008; 45(1):45-52.

12. Tachibana M, Mizukoshi O, Harada Y, Kawamoto K, Nakai Y. A multi-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling. Pharamatherapeutica. 1984; 3(8):526-30.

13. Nakamura S, Hashimoto Y, Mikami M, Yamanaka E, Soma T, Hino M, Azuma A, Kudoh S. Effect of the proteolytic enzyme serrapeptase in patients with chronic airway disease. Respirology. 2003; 8(3):316-20.

14. Mazzone A, Catalani M, Costanzo M, Drusian A, Mandoli A, Russo S, Guarini E, Vesperini G. Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicenter, double-blind, randomized trial versus placebo. J Int Med Res. 1990; 18(5):379-88.

15. Sannino G, Gigola P, Puttini M, Pera F, Passariello C. Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis. Int J Immunopathol Pharmcol. (2013). 26(3): 825-31.

16. Mecikoglu M, Saygi B, Yildirim Y, Karadaq-Sayqi E, Ramadan SS, Esemenli T. The effect of proteolytic enzyme serratiopeptidase in the treatment of experimental implant-related infection. J Bone Joint Surg Am. 2006; 88(6):1208-14.

17. Craigen B, Dashiff A, Kadouri DE. The use of commercially available alpha-amylase compounds to inhibit and remove Staphylococcus aureus biofilms. The Open Microbiology J (2011). 5:21-31.

18. Chaignon P, Sadovskaya I, Ragunah C, Ramasubbu N, Kaplan JB, Jabbouri S. Susceptibility of staphylococcal biofilms to enzymatic treatments depends on their chemical composition. Appl Microbiol Biotechnol (2017). 75:125-132.

19. Parry MF, Neu HC. Effect of N-acetylcysteine on antibiotic activity and bacterial growth in vitro. J Clin Microbiol. (1977). 5(1):58-61.

20. Cevik K, Ulusoy S. Inhibition of Pseudomonas aeruginosa biofilm formation by 2,2’-bipyridyl, lipoic, kojic and picolinic acids. Iran J Basic Med Sci (2015). 18(8):758-763.

Manufactured by Naturo Aid Pharmaceutical Inc. in accordance with Good Manufacturing Practices | NHPD-GMP site license #300391#302-20285 Stewart Crescent, Maple Ridge, BC, V2X 8G1, Canada

Canada & US: 1-800-490-1738 | Other: 1-604-465-1688 | Fax: 1-604-465-1299Email: info@vitaaid.com | Fore more information, please visit our website: www.vitaaid.com

For Education Purpose Only: The entire 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. All statements in this article have not been evaluated by the Food and Drug Administration and are not intended to be used to diagnose, treat, or prevent any diseases.