ProBio PCC

Healthcare Professional Product Guide

Probiotic dietary supplement to help maintain a healthy
gastroinestinal environment.*
Scientifically Tested for Safety and Efficacy.
This is an educational publication provided to
help licensed healthcare professionals understand
the science upon which ProBio PCC is based
and the mechanisms of action by which ProBio
PCC works in the body. This guide should
not be used to sell ProBio PCC and is
intended for healthcare professionals only.
The only claims that can be made for
ProBio PCC are those that have been
approved by the Company.

Maintains a Healthy Gastrointestinal Environment*

LACTOBACILLUS FERMENTUM PCC

A Scientific Product Review

by Josh Zhu, M.D., Ph.D. and Michael Chang, Ph.D.

* These

statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

ProBioPCC

TM

Maintains a Healthy Gastrointestinal Environment*

Introduction
ProBio PCC is a probiotic dietary supplement
developed and manufactured by Pharmanex, LLC to help
relieve symptoms associated with gastrointestinal (GI)
malaise, bowel irregularity, irritable bowel syndrome (IBS),
diarrhea, and other digestive and non-digestive discomforts.
Pharmanex unique strain of Lactobacillus was isolated
from a Swedish woman who showed an extraordinary
resilience to food poisoning organisms. This unique
patentpending strain of Lactobacillus, Lactobacillus
fermentum, has the ability to survive passage through the
harsh environment of the stomach and has the ability to
colonize the intestine. Subsequent clinical research has
shown a decrease in gastrointestinal problems and an
increase in the growth of beneficial bacteria in the digestive
tract after the introduction of this particular bacteria strain.
ProBio PCC is carefully manufactured to ensure product
stability and that a significant number of active or live
cultures are delivered to the lower digestive system for
maximum benefit.
This Technical Product Bulletin discusses the importance of a healthy gastrointestinal tract and the scientific
rationale behind the formulation of ProBio PCC. It also
discusses the purported health benefits, mechanisms of
action, scientific studies, and proprietary processing. This
is an educational bulletin provided to help licensed healthcare professionals understand the science upon which
ProBio PCC is based. This bulletin should not be used
to sell ProBio PCC, and it should be distributed only to
licensed healthcare professionals. The only claims that
can be made for ProBio PCC are those that have been
approved by the Company.

Your Digestive Defense System

An important component of your digestive defense

system is a variety of friendly bacteria, often referred to as
gastrointestinal microflora, that aid digestion and enhance
your bodys own digestive immune response to pathogens.
The healthy proliferation of these friendly organisms makes
it less likely that undesirable bacteria can grow in the
digestive tract. As we encounter challenges to our digestive
system we can severely disturb the delicate balance of our
bodys intestinal flora and our digestive immune system
can be compromised.
Maintaining your intestinal ecosystem is an essential,
yet often overlooked part of healthy living. Friendly and
pathogenic bacteria form a delicate, yet dynamic balance
as they compete to adhere and colonize the mucosa of
the digestive tract. Both friendly and pathogenic bacteria
can be affected by changes in the intestinal environment.
Stress, infections, antibiotics, stress, traveling, alcohol
consumption, and a poor diet can disturb the delicate
balance of our digestive tract. This often results in a
decreased number of friendly bacteria while allowing
pathogenic bacteria to gain a foothold. Your body is also
frequently exposed to harmful pathogensoften consumed
with your foodwhich can cause occasional gastrointestinal
(GI) malaise, bowel irregularity, diarrhea, and other digestive
and non-digestive discomforts.
Bacterial colonization of the gut begins at birth as
newborns are maintained in a sterile status until the delivery
begins, and continues throughout life with notable age
specific changes (Mitsuoka 1992). By the time we are
adults, there are more than 400 different bacterial species
and over 100 trillion total bacteria in the human digestive
tract (Tannock 1999). The number of bacteria found in
the digestive tract is approximately 10 times the number
of cells found in the rest of the body and account for
nearly two pounds of body weight (Mitsuoka 1992). The
density of bacteria in the intestinal flora increases dramatically from a relatively low concentration in the stomach
(104 CFU/ml) to a high concentration in the colon
(1012 CFU/ml). These bacteria have been estimated to
account for nearly half of the volume of the contents in
the colon. (Holzapfel 1998).
The gastrointestinal microflora influence our nutritional, physiological, and protective processes, providing
both direct and indirect defense functions in our body.
They aid digestion by breaking down proteins, carbohydrates and fats in food, and help absorption of necessary
nutrients such as minerals, amino acids and vitamins.
The microflora also directly prevent colonization by
harmful pathogens by competing for essential nutrients
and adherence to the mucosal epithelium of the digestive
tract. In addition, by producing inhibitory substances,
such as short-chain fatty acids, hydrogen peroxide, and
antimicrobial compounds, the microflora also create an
intestinal environment that is generally unfavorable for
the growth of harmful pathogens. These compounds

* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

may reduce not only the number of viable pathogens but

may also affect bacterial metabolism and toxin production
(Mackie 1999).

Probiotic efficacy

A healthy balance of intestinal flora can be restored

through the consumption of food or food supplement
products that contain friendly live bacteria cultures,
commonly known as probiotics (FAO/WHO 2001).
Lactobacillus bacteria were first identified by Louis Pasteur,
but the original observation of the positive role of probiotic
bacteria is attributed to Eli Metchnikoff, the Russian
Scientist working at the Pasteur Institute, who received
the Nobel Prize in the early 1900s for his discoveries.
Metchnikoff suggested that, The dependence of the
intestinal microbes on the food makes it possible to adopt
measure to modify the flora in our bodies and to replace
the harmful microbes by useful microbes (Metchnikoff
1907). A modern day definition of a probiotic could be
stated as a preparation of or a product containing viable,
defined microorganisms in sufficient numbers, which alter
the microflora (by implantation or colonization) in a
compartment of the host and by that exert beneficial
effects in this host. (Havenaar 1992).
Probiotics containing Lactobacillus have been found
in the human diet for centuries. Folk remedies since the
beginning of recorded history have ascribed beneficial
effects to yogurts and cheeses Even before antibiotics
became a mainstream, probiotics were studied for their
ability to increase the growth rate of farm animals and
impart protection to these animals against viruses and
pathogenic bacteria. Probiotics are used in fermented
milk products and food preservatives, but it has been
only during the past two decades that advances in science
and technology have enabled identification of specific
strains of Lactobacillus with unique properties offering
improved health benefits. It has been determined that
different strains of probiotic bacteria may exert different
effects based on specific capabilities and activities, even
within one species (Ouwehand 1999, Bernet 1993).
In a recent report of a joint Food and Agriculture
Organization of the United Nations/World Health
Organization (FAO/WHO) expert consultation, guidelines
for the assessment of probiotics were outlined in order to
assess individual probiotic properties (FAO/WHO 2001).

The consultation suggested the following guidelines

regarding pH survival, colonization, identity, and dosing.
1. pH Survival. Probiotics should survive passage
through the digestive tract. This means they must be
resistant to gastric juices and bile, or be consumed in a
food vehicle that allows them to survive passage
through the stomach and exposure to bile.
2. Colonization. Probiotics should also have the capability to proliferate and colonize in the gut and be able to
grow in the presence of bile under conditions in the
intestines. Probiotics must be able to exert their benefits on the host through growth and/or activity in the
human body. The ability of the probiotic to remain
viable in the intestines and remain effective should be
verified.
Different microorganisms express habitat preferences
that may differ from person to person, resulting in
varying levels of mucosal adherence (Freter 1992).
Lactobacilli are among the indigenous flora colonizing
the lower intestines. Bacteria colonizing such hightransit-rate sites must adhere firmly to the mucosal
epithelium and must adapt to the environment of this
adhesion site. The competition for adhesion receptors
between probiotic and undesirable microorganisms,
therefore, is dependent on such habitat preferences
(Savage 1972, Beachey 1980).
3. Identity. The probiotics should be gram-positive bacteria, primarily in two genera, Lactobacillus or
Bifidobacterium. The identity of the strain according to
the International Code of Nomenclature and the
viable concentration of each probiotic at the end of shelf
life should be stated on the label.
4. Dosing. The product must indicate the dosage regimens and duration of use as recommended by the
manufacturer and should be based on scientific evidence. Probiotics should be ingested regularly for the
health promoting properties to persist.

Lactobacillus fermentum PCC

In developing ProBio PCC, Pharmanex has followed
the probiotic guidelines as established by the FAO/WHO
expert consultation for pH survival, colonization, identity,
and dosing (FAO/WHO 2001). ProBio PCC provides a
proprietary strain of friendly bacteria (Lactobacillus fermentum PCC) that has been shown to be resistant to an
acidic environment and can effectively colonize the lower
digestive tract. Pharmanexs unique strain of Lactobacillus
was isolated from a Swedish woman (Gibson 1994).
Researchers then developed a method in which they were
able to grow L. fermentum commercially by using bacterial
cell culture technology in a special nutrient medium. Each
ProBio PCC capsule is guaranteed to contain a minimum
of two billion CFUs (colony forming units) of the proprietary strain L.Fermentum PCC at the end of shelf life.

* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Health Benefits
Pharmanex ProBio PCC relieves symptoms associated with gastrointestinal (GI) malaise, bowel irregularity,
irritable bowel syndrome (IBS), diarrhea, and other digestive
and nondigestive discomforts. Clinical research has
shown a decrease in gastrointestinal problems and an
increase in the growth of beneficial bacteria in the digestive
tract after the introduction of this particular bacteria strain.
ProBio PCC has been clinically proven to encourage
the proliferation of healthy probiotic bacteria in the lower
digestive tract, thus helping to fortify the natural digestive
defense system (Welin 2002). By actively colonizing the
lower digestive tract, ProBio PCC may be able to discourage the development of pathogenic bacteria, yeast,
and urinary tract infections. This effect may be due to
direct action, modulation of local immunity, modifications
of the intestinal ecosystem or a combination of these
effects (Marteau 1998).

Clinical Evidence of Efficacy

The primary goal of probiotic therapy is to restore the
natural balance of intestinal microflora in order to have
an optimally functioning digestive defense system; this
effect is well established in published research (FAO/WHO
2001). Independent research on probiotics, including
Lactobacillus strains, have confirmed the following primary
outcomes of probiotic therapy: (1) restoration of a healthy
intestinal microflora; (2) stimulation of mucosal immunity;
(3) improvement in gastrointestinal disturbances, including
frequency and duration of diarrhea associated with antibiotics, enteropathogens, and travelers diarrhea; and (4)
improvement in urogenital microflora.
Mucosal Immunity
The digestive tract provides a protective interface
between our internal environment and a constantly challenging external environment. Approximately 70% of the
human immune system is localized in the digestive tract
(Bengmark 2001). The surface of the intestinal mucosal
membranes is protected by a local adaptive immune system, characterized by gut-associated lymphoid tissue.
This gut-associated lymphoid tissue represents the largest
mass of lymphoid tissue in the human body. It has been
proposed that the generation of gut-associated lymphoid
tissue and our intestinal immune regulation depends to
a large extent on the establishment of indigenous microflora
(Isolauri 2001). Probiotic bacteria have been shown to
enhance humoral immune responses and thereby promote
the intestines immunologic barrier. Furthermore, probiotic
bacteria have been shown to stimulate humoral immune
responses to enteropathogens, thus aiding in elimination,
and to modulate the hosts immune responses to potentially
harmful antigens (Kaila 1992, Perdigon 1986).

Alterations to the intestinal microflora have been implicated

in immunological disturbances, including food allergy,
atopic eczema, and irritable bowel diseases, such as
Irritable Bowel Syndrome (IBS) and pouchitis (Majamaa
1997, Isolauri 2000, Shanahan 2000). To date no causative
agent of IBS has been identified and no satisfactory therapy
has been reported. IBS is a disorder of the motility of the
intestine and can manifest itself as diarrhea, constipation,
alternative travelers diarrhea, flatulence, bloating, and
abdominal pain. There is a high incidence of IBS in Western
society up to 30% suffering to some extent (Li 2002).
Some studies support the potential role of probiotics in
therapy and prophylaxis of inflammatory bowel disease
by modulating the intestinal microflora (Gionchetti
2002, Gupta 2000).
Gastrointestinal Disturbances
According to the World Health Organization, up to
30% of the population, even in developed countries, are
affected by foodborne diarrhea each year (FAO/WHO
2001). Strong in vitro evidence and some animal studies
show that certain probiotic strains can inhibit the growth
and adhesion of a range of enteropathogens (Coconnier,
1997, Hudault 1997, Gopal 2001, Ogawa 2001).
Another major cause of diarrhea is caused by an imbalance
of the intestinal microflora and a proliferation of
enteropathogens associated with antibiotic therapy
(FAO/WHO 2001, Schrezenmeir 2001). According to
Marteau, diarrhea occurs in approximately 20% of patients
who receive antibiotics (Marteau 2001). Clostridium difficile,
an enteropathogen, is not uncommon in a healthy intestinal
tract, but the disruption of the indigenous microflora by
antibiotics leads to an abnormal elevation of their numbers,
and subsequent symptoms related to toxin production
(Marteau 2001). Probiotics have been shown to be useful
during antibiotic therapy, and may also help alleviate the
signs and symptoms once antibioticinduced diarrhea has
occurred (Arvola 1999, Armuzzi 2001).
Urogenital Disturbances
The urogenital microflora of a healthy woman comprises
more than 50 species of organisms, which differ in composition according to reproductive stages and exposure
to several factors, including antibiotics and spermicides.
Urinary tract infections are very common with more than
300 million cases of urinary tract infections, bacterial
vaginosis, and yeast vaginitis woldwide each year (Reid
2001). Studies investigating the effects of probiotics on
the restoration of a healthy urogenital microflora have
had mixed results; it appears that certain properties of
these strains, including adhesive ability and production
of inhibitory substances are important in conferring protection to the host (Reid 2001, FAO/WHO 2001).

Many probiotic effects are mediated through immune

regulation, by balancing inflammatory substances, normalizing mucosal function, and maintaining normal intestinal
permeability (Isolauri, 2001, Kalliomaki 2001).
3

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Pre-Clinical StudiesL. fermentum PCC

L. fermentum PCC has been shown in animal studies
to have immuno-modulating and anti-fungal activity, while
the anti-bacterial activity seen in laboratory studies have
been confirmed in animal model studies for some pathogens.
Pre-clinical studies have shown that L. fermentum
PCC is stable and that the strain can survive transit
through the digestive tract. Colonization of the human
digestive tract has been demonstrated after a single dose;
the duration of colonization varied between individuals
with a mean value of 14 days (Gibson 1994).
Adhesion and colonization of the human digestive
tract has been indicated as a key criterion for selection of probiotics. L. fermentum PCC has been shown both in vitro
and in vivo to adhere to the human intestinal mucosa. An
investigative study in which intestinal mucosal samples
were treated with PCC-specific antiserum, showed that
L. fermentum PCC was associated with the small intestinal
mucosa after oral administration. The investigators proposed
that this attachment could allow prolonged colonization
of the entire tract and contribute to the probiotic effectiveness
of this strain. The mucosal attachment could also contribute
to the observed immunomodulation observed in other
studies (Welin 2002). (see graph)

There is emerging evidence that strains of Lactobacillus

bacteria that have the capacity to associate with the Peyers
Patch (an area of mucosal lymphoid tissue in the small
intestine) have a greater potential to trigger the mucosal
immune system. Researchers have found that L. fermentum
PCC preferentially targeted, and was recovered from, the
Peyers Patch in mice; hence, L. fermentum PCC could have
an enhanced capacity to trigger the mucosal immune
system (Plant 2002). (see graph)

Clinical StudiesL. fermentum PCC

The health benefits of L. fermentum PCC are documented
in human, animal, and in vitro studies. Twelve clinical
studies have been completed, or are in progress, validating
the stability, colonization, and clinical efficacy of L. fermentum PCC. Additional clinical studies are currently in

progress. This proprietary strain has been shown in clinical

studies to prevent the development of diarrhea, and reduce
the symptoms of irritable bowel syndrome, including
diarrhea, constipation, flatulence, bloating, and abdominal
pain (Conway 2002, Li 2002). Sixteen animal and in vitro
studies have been completed on this proprietary strain,
documenting similar positive results.
A number of probiotic preparations have been evaluated
for their efficacy in preventing travelers diarrhea, but those
reported to date have had limited success with small
improvements noted. To determine the effects of L. fermentum on travelers diarrhea, 300 Swedish soldiers travelling to Lebanon were given L. fermentum three days prior
to departure and for four weeks on location. In this study,
a statistically significant reduction (50%) in the incidence
of gastrointestinal disturbances and diarrhea was noted.
Furthermore, those subjects that received the L. fermentum
PCC had less severe symptoms than those who received
L. acidophilus or placebo (Conway 2002). (see graph)

A crossover, single-blind, placebo controlled study was

initiated to evaluate the effects of L. fermentum on fecal
microbes and symptoms in patients with Irritable Bowel
Syndrome (IBS). L. fermentum administered together with
resistant starch resulted in an improvement in symptoms
when compared to placebo and baseline results. The fecal
microbial population was correlated with symptoms and
it was shown that the pathogenic bacteria were consistently
high when symptoms were more severe. It is also interesting
to note that in laboratory fermentation studies, it has been
shown that these enteric bacteria were reduced when L. fermentum was added to the fermentation vessel, alone or in
combination with a high amylose resistant starch (Li 2002).

Proprietary Processing
The combination of quality ingredients, qualified
manufacturers, certified independent laboratory verification,
and a continuous drive to supply leading edge products,
ensure our consumers the highest quality products available in the industry. ProBio PCC has been developed
through scientific and analytical methods to ensure that
the product meets label claims for live cultures (CFUs) at
the end of shelf life, which is a more valid indicator of
efficacy than claiming number of live cultures at manufacturing. Pharmanex has established an exclusive supply
agreement with the supplier of L. fermentum PCC, making
this unique strain proprietary to our company. L. fermentum
PCC is a patent-pending strain of Lactobacillus bacteria
with ten patents having been filed to date. In developing

**These
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statementshave
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bythe
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ProBio PCC
, Pharmanex has followed the probiotic
guidelines as established by the FAO/WHO expert consultation for pH survival, colonization, identity, and
dosing (FAO/WHO 2001).
The ingredients in ProBio PCC have been tested
for purity, and where applicable, ingredients are certified
pure by testing for unwanted microbes, including Salmonella,
E. coli, other coliforms, and Staphylococcus aureus. Additional
tests include total plate counts, yeasts, molds and pesticide
residues. Our manufacturers go through a detailed selection
and certification process to assure their compliance with
Good Manufacturing Practice (GMP) standards set by the
Food and Drug Administration (FDA).

Side Effects
There are no known side effects at the recommended
dosage.

Safety and Toxicity

ProBio PCC is safe and well tolerated at the recommended dosage. Lactobacilli have a long history of use as
probiotics without established risk to humans, which
remains the best proof of safety (Naidu 1999, FAO/WHO
2001). Also no pathogenic or virulent properties have
been found (Aguirre 1993). Probiotics containing
Lactobacillus have been shown to be safe in children
(FAO/WHO 2001).

Contraindications/Drug Interactions
If you are pregnant or lactating, or taking a prescription
medication, consult a physician prior to use. There are no
known drug interactions, with the exception of antibiotics
as mentioned above.

Directions for Use

ProBio PCC is recommended for adults who experience occasional diarrhea, constipation, or cramps as a
result of distressed digestive flora, and for adults who
experience occasional gastrointestinal disturbances such
as gas or bloating. Take one capsule daily to maintain
normal digestive health. While L. fermentum has been
shown to actively colonize the lower digestive tract, continuous ingestion it is recommended for best results.

How Supplied
ProBio PCC is supplied in a 30 day supply of
30 capsules.

Storage
Store in a cool, dry place. Avoid excessive heat. Protect
from light. This product does not require refrigeration.

Shelf Life
Expiration date and lot code numbers are stamped
on the bottle.

Warnings
Keep out of reach of children. If you are pregnant
or nursing, or taking a prescription medication, consult
a physician before using this product.

References
1. Aguirre M, Collins MD. J Appl Bacteriol 1993;75:95107.
2. Armuzzi A, et al. Aliment Pharmacol Ther
2001;15(2):163169.
3. Arvola T, et al. Pediatrics 1999;104(5):14.
4. Beachey EH. Bacterial adherence. London: Chapman and
Hall, 1980.
5. Bengmark S. Pre-, pro- and synbiotics. Curr Opin Clin
Nutr Metab Care 2001;4(6):5719.
6. Bernet MF, Brassart D, Neeser JR, Servin AL. Appl Environ
Microbiol 1993;59:412131.
7. Coconnier MH, et al. Antibacterial effect of the adhering
human Lactobacillus acidophilus strain LB. Antimicrob
Agents Chemother 1997;41:104652.
8. Conway PL, Blomberg L. Reduction in incidence and
severity of diarrhoea in soldiers consuming Lactobacillus
fermentum KLD. Publication in preparation (in file), 2002.
9. Freter R. Factors affecting the microecology of the gut. In:
Fuller R, ed. Probiotics, the scientific basis. London:
Chapman & Hall, 1992: 11144.
10. Gibson SAW, Conway PL. Recovery of a probiotic organism from human faeces after oral dosing. In Human
Health: The contribution of microorganisms in Springer
Series in Applied Biology, 1994, pp. 119143.
11. Gionchetti P, et al. Gastroenterol 2000;119:3059.
12. Gopal PK, et al. Int Food Microbiol 2001;97(3):207216.
13. Gupta P, et al. J Pediatr Gastroenterol Nutr 2000;31:4537.
14. Havenaar R, Huis Int Veld MJH. Probiotics: a general view.
In: Lactic acid bacteria in health and disease. Volume 1.
Amsterdam: Elsevier Applied Science Publishers, 1992.
15. Holzapfel WH, Haberer P, et al. Overview of gut flora and
probiotics. In J Food Microbiol 1998;41:85101.
16. Hudault S, et al. Appl Environ Microbiol 1997;63:513518.
17. Isolauri E, et al. Clin Exp Allergy 2000;30:160510.
18. Isolauri E, et al. Probiotics: effects on immunity. Am J Clin
Nutr 2001;73(suppl):444S50S.
19. Joint FAO/WHO Expert consultation on evaluation of
health and nutritional properties of probiotics in food
including powder milk with live lactic acid bacteria.
Crdoba, Argentina. October 14, 2001.
20. Kaila M, et al. Enhancement of the circulating antibody
secreting cell response in human diarrhea by a human lactobacillus strain. Pediatr Res 1992;32:1414.
21. Kalliomaki M, et al. Lancet 2001;357:10769.
22. Li P, Conway PL. Publication in preparation (in file), 2002.
23. Mackie R, Gaskins HR. Gastrointestinal microbial ecology.
Science & Medicine, Nov / Dec 1999.
24. Majamaa H, Isolauri E. J Allergy Clin Immunol
1997;99:17986.
25. Marteau P, Rambaud JC. Probiotiques en gastroenerologie:
bases rationelles, effet demontres et perspectives. HepatoGastro 1998;5:267273.
26. Marteau PR, et al. Protection from gastrointestinal disease with
the use of probiotics. Am J Clin Nutr 2001;73(suppl):430S6S.
27. Metchnikoff E. Lactic acid as inhibiting intestinal putrefaction. In The prolongation of life: optimistic studies. W.
Heinemann, London, pg. 161183. 1907.

* These
statements
Foodand
andDrug
Drug
Administration.This
product
is intended
not intended
to diagnose,
treat,orcure
or prevent
any disease.
* These
statementshave
havenot
notbeen
beenevaluated
evaluated by the Food
Administration.
This product
is not
to diagnose,
treat, cure
prevent
any disease.

28. Mitsuoka T. Intestinal flora and ageing. Nutr Rev

1992;50:43846.
29. Naidu AS, Biblack WR, Clemens RA. Probiotic spectra of
lactic acid bacteria (LAB). Crit Revs Food Sci & Nutr
1999;(39):13126.
30. Ogawa M, et al. Infect Immun 2001;69:11018.
31. Ouwehand AC, Kirjavainen PV, Grnland MM, Isolauri E,
Salminen SJ. Adhesion of probiotic microorganisms to
intestinal mucus. Int Dairy J 1999;9:62330.
32. Perdigon G, et al. Effect of perorally administered lactobacilli on macrophage activation in mice. Infect Immun
1986;53:40410.
33. Plant L, Conway PL. Association of Lactobacillus spp with
Peyers Patches in mice. Clinical and Diagnostic
Immunology 2002;8(2):320324.
34. Reid G. Am J Clin Nutr 2001:73(suppl):437S43S.
35. Savage DC. Associations and physiological interactions of
indigenous microorganisms and gastrointestinal epithelia.
Am J Clin Nutr 1972;25:13729.
36. Schrezenmeir J, de Vrese M. Probiotics, prebiotics, and
synbiotics approaching a definition. Am J Clin Nutr
2001;73(suppl):361S4S.
37. Shanahan F. Inflamm Bowel Dis 2000;6:10715.
38. Tannock GW. Analysis of the intestinal microflora: A
renaissance. Antonie van Leenwenhoek
1999;76:265278.
39. Welin A, Farthing M, Conway PL. Publication in preparation (in file), 2002.

* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

The Pharmanex 6S Quality Process

Central to the Pharmanex mission of transforming time-honored, traditional preparations into health promoting botanical products with known content and consistent activity is the Pharmanex 6S Quality Process.

Selection

Exhaustive scientific review of research and databases is conducted.

Authenticity, usefulness, and safety standards are determined.

Sourcing

Teams of experts investigate potential sources and evaluate quality.

Comprehensive botanical and chemical evaluations are completed.

Structure

Structural analyses of natural compounds are determined.

Active ingredients are isolated and studied.

Standardization

Strict standardization to at least one relevant marker molecule is required.

Proprietary processing methods to increase consistency and ensure measured dose

effectiveness are developed.

Safety

Safety is assessed from available research.

Microbial test, chemical, toxin, and heavy metal analyses are conducted.

Substantiation

Documented pre-clinical and clinical studies are reviewed.

Pharmanex sponsored studies are initiated when appropriate.

For More Information:

To learn more about the Pharmanex line of natural healthcare products, please call
Product Support 1-800-487-1000.
Visit our website and access information directly at www.pharmanex.com

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