Probio PCC

8/10/2019 Probio PCC

1/8

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

Healthcare Professional Product Guide

Probiotic dietary supplement to help maintain a healthygastroinestinal environment.*

Scientifically Tested for Safety and Efficacy.

A Scientific Product Reviewby Josh Zhu, M.D., Ph.D. and Michael Chang, Ph.D.

LACTOBACILLUS FERMENTUM PCC

Maintains a Healthy Gastrointestinal Environment*

ProBio PCC

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

PCCworks in the body. This guide shouldnot 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.


2/8

An important component of your digestive defensesystem is a variety of friendly bacteria, often referred to asgastrointestinal microflora, that aid digestion and enhanceyour bodys own digestive immune response to pathogens.The healthy proliferation of these friendly organisms makesit less likely that undesirable bacteria can grow in thedigestive tract. As we encounter challenges to our digestivesystem we can severely disturb the delicate balance of ourbodys 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 andpathogenic bacteria form a delicate, yet dynamic balanceas they compete to adhere and colonize the mucosa ofthe digestive tract. Both friendly and pathogenic bacteriacan be affected by changes in the intestinal environment.Stress, infections, antibiotics, stress, traveling, alcoholconsumption, and a poor diet can disturb the delicatebalance of our digestive tract. This often results in adecreased number of friendly bacteria while allowingpathogenic bacteria to gain a foothold. Your body is alsofrequently exposed to harmful pathogensoften consumedwith your foodwhich can cause occasional gastrointestinal(GI) malaise, bowel irregularity, diarrhea, and other digestiveand non-digestive discomforts.

Bacterial colonization of the gut begins at birth asnewborns are maintained in a sterile status until the deliverybegins, and continues throughout life with notable agespecific changes (Mitsuoka 1992). By the time we areadults, there are more than 400 different bacterial speciesand over 100 trillion total bacteria in the human digestivetract (Tannock 1999). The number of bacteria found inthe digestive tract is approximately 10 times the numberof cells found in the rest of the body and account fornearly two pounds of body weight (Mitsuoka 1992). Thedensity of bacteria in the intestinal flora increases dramati-cally 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 toaccount for nearly half of the volume of the contents inthe colon. (Holzapfel 1998).

The gastrointestinal microflora influence our nutri-tional, physiological, and protective processes, providingboth direct and indirect defense functions in our body.They aid digestion by breaking down proteins, carbohy-drates and fats in food, and help absorption of necessarynutrients such as minerals, amino acids and vitamins.The microflora also directly prevent colonization byharmful pathogens by competing for essential nutrientsand adherence to the mucosal epithelium of the digestivetract. In addition, by producing inhibitory substances,such as short-chain fatty acids, hydrogen peroxide, andantimicrobial compounds, the microflora also create anintestinal environment that is generally unfavorable forthe growth of harmful pathogens. These compounds

IntroductionProBio PCC is a probiotic dietary supplementdeveloped and manufactured by Pharmanex, LLC to helprelieve 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 isolatedfrom a Swedish woman who showed an extraordinaryresilience to food poisoning organisms. This uniquepatentpending strain of Lactobacillus, Lactobacillusfermentum, has the ability to survive passage through theharsh environment of the stomach and has the ability tocolonize the intestine. Subsequent clinical research has

shown a decrease in gastrointestinal problems and anincrease in the growth of beneficial bacteria in the digestivetract after the introduction of this particular bacteria strain.ProBio PCC is carefully manufactured to ensure productstability and that a significant number of active or livecultures are delivered to the lower digestive system formaximum benefit.

This Technical Product Bulletin discusses the impor-tance of a healthy gastrointestinal tract and the scientificrationale behind the formulation of ProBio PCC. It alsodiscusses the purported health benefits, mechanisms ofaction, scientific studies, and proprietary processing. This

is an educational bulletin provided to help licensed health-care professionals understand the science upon whichProBio PCC is based. This bulletin should not be usedto sell ProBio PCC, and it should be distributed only tolicensed healthcare professionals. The only claims thatcan be made for ProBio PCC are those that have beenapproved by the Company.

Your Digestive Defense System

Maintains a Healthy Gastrointestinal Environment*

ProBioPCCTM

* 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.1


3/8

may reduce not only the number of viable pathogens butmay also affect bacterial metabolism and toxin production(Mackie 1999).

Probiotic efficacy

A healthy balance of intestinal flora can be restoredthrough the consumption of food or food supplementproducts 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 probioticbacteria is attributed to Eli Metchnikoff, the RussianScientist working at the Pasteur Institute, who receivedthe Nobel Prize in the early 1900s for his discoveries.Metchnikoff suggested that, The dependence of theintestinal microbes on the food makes it possible to adoptmeasure to modify the flora in our bodies and to replacethe harmful microbes by useful microbes (Metchnikoff1907). A modern day definition of a probiotic could bestated as a preparation of or a product containing viable,defined microorganisms in sufficient numbers, which alterthe microflora (by implantation or colonization) in acompartment of the host and by that exert beneficialeffects in this host. (Havenaar 1992).

Probiotics containing Lactobacillus have been foundin the human diet for centuries. Folk remedies since thebeginning of recorded history have ascribed beneficialeffects to yogurts and cheeses Even before antibioticsbecame a mainstream, probiotics were studied for theirability to increase the growth rate of farm animals andimpart protection to these animals against viruses andpathogenic bacteria. Probiotics are used in fermentedmilk products and food preservatives, but it has beenonly during the past two decades that advances in scienceand technology have enabled identification of specific

strains of Lactobacillus with unique properties offeringimproved health benefits. It has been determined thatdifferent strains of probiotic bacteria may exert differenteffects based on specific capabilities and activities, evenwithin one species (Ouwehand 1999, Bernet 1993).

In a recent report of a joint Food and AgricultureOrganization of the United Nations/World HealthOrganization (FAO/WHO) expert consultation, guidelinesfor the assessment of probiotics were outlined in order toassess individual probiotic properties (FAO/WHO 2001).

The consultation suggested the following guidelinesregarding pH survival, colonization, identity, and dosing.

1. pH Survival. Probiotics should survive passagethrough the digestive tract. This means they must beresistant to gastric juices and bile, or be consumed in afood vehicle that allows them to survive passagethrough the stomach and exposure to bile.

2. Colonization. Probiotics should also have the capabil-ity to proliferate and colonize in the gut and be able togrow in the presence of bile under conditions in theintestines. Probiotics must be able to exert their bene-fits on the host through growth and/or activity in thehuman body. The ability of the probiotic to remainviable in the intestines and remain effective should beverified.

Different microorganisms express habitat preferencesthat may differ from person to person, resulting invarying levels of mucosal adherence (Freter 1992).Lactobacilli are among the indigenous flora colonizing

the lower intestines. Bacteria colonizing such high-transit-rate sites must adhere firmly to the mucosalepithelium and must adapt to the environment of thisadhesion site. The competition for adhesion receptorsbetween probiotic and undesirable microorganisms,therefore, is dependent on such habitat preferences(Savage 1972, Beachey 1980).

3. Identity. The probiotics should be gram-positive bac-teria, primarily in two genera, Lactobacillus orBifidobacterium. The identity of the strain according tothe International Code of Nomenclature and theviable concentration of each probiotic at the end of shelf

life should be stated on the label.

4. Dosing. The product must indicate the dosage regi-mens and duration of use as recommended by themanufacturer and should be based on scientific evi-dence. Probiotics should be ingested regularly for thehealth promoting properties to persist.

Lactobacillus fermentum PCCIn developing ProBio PCC, Pharmanex has followed

the probiotic guidelines as established by the FAO/WHOexpert consultation for pH survival, colonization, identity,and dosing (FAO/WHO 2001). ProBio PCC provides a

proprietary strain of friendly bacteria (Lactobacillus fer-mentum PCC) that has been shown to be resistant to anacidic environment and can effectively colonize the lowerdigestive tract. Pharmanexs unique strain of Lactobacilluswas isolated from a Swedish woman (Gibson 1994).Researchers then developed a method in which they wereable to grow L. fermentum commercially by using bacterialcell culture technology in a special nutrient medium. EachProBio PCC capsule is guaranteed to contain a minimumof two billion CFUs (colony forming units) of the propri-etary 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. 2


4/8

Alterations to the intestinal microflora have been implicatedin immunological disturbances, including food allergy,atopic eczema, and irritable bowel diseases, such asIrritable Bowel Syndrome (IBS) and pouchitis (Majamaa1997, Isolauri 2000, Shanahan 2000). To date no causativeagent of IBS has been identified and no satisfactory therapyhas been reported. IBS is a disorder of the motility of theintestine and can manifest itself as diarrhea, constipation,alternative travelers diarrhea, flatulence, bloating, and

abdominal pain. There is a high incidence of IBS in Westernsociety up to 30% suffering to some extent (Li 2002).Some studies support the potential role of probiotics intherapy and prophylaxis of inflammatory bowel diseaseby modulating the intestinal microflora (Gionchetti2002, Gupta 2000).

Gastrointestinal DisturbancesAccording to the World Health Organization, up to

30% of the population, even in developed countries, areaffected by foodborne diarrhea each year (FAO/WHO2001). Strong in vitro evidence and some animal studiesshow that certain probiotic strains can inhibit the growthand adhesion of a range of enteropathogens (Coconnier,1997, Hudault 1997, Gopal 2001, Ogawa 2001).

Another major cause of diarrhea is caused by an imbalanceof the intestinal microflora and a proliferation ofenteropathogens associated with antibiotic therapy(FAO/WHO 2001, Schrezenmeir 2001). According toMarteau, diarrhea occurs in approximately 20% of patientswho receive antibiotics (Marteau 2001). Clostridium difficile,an enteropathogen, is not uncommon in a healthy intestinaltract, but the disruption of the indigenous microflora byantibiotics leads to an abnormal elevation of their numbers,and subsequent symptoms related to toxin production(Marteau 2001). Probiotics have been shown to be usefulduring antibiotic therapy, and may also help alleviate thesigns and symptoms once antibioticinduced diarrhea hasoccurred (Arvola 1999, Armuzzi 2001).

Urogenital DisturbancesThe urogenital microflora of a healthy woman comprises

more than 50 species of organisms, which differ in com-position according to reproductive stages and exposureto several factors, including antibiotics and spermicides.Urinary tract infections are very common with more than300 million cases of urinary tract infections, bacterialvaginosis, and yeast vaginitis woldwide each year (Reid2001). Studies investigating the effects of probiotics onthe restoration of a healthy urogenital microflora havehad mixed results; it appears that certain properties ofthese strains, including adhesive ability and productionof inhibitory substances are important in conferring pro-tection to the host (Reid 2001, FAO/WHO 2001).

Health BenefitsPharmanex ProBio PCC relieves symptoms associ-

ated with gastrointestinal (GI) malaise, bowel irregularity,irritable bowel syndrome (IBS), diarrhea, and other digestiveand nondigestive discomforts. Clinical research hasshown a decrease in gastrointestinal problems and anincrease in the growth of beneficial bacteria in the digestivetract after the introduction of this particular bacteria strain.ProBio PCC has been clinically proven to encouragethe proliferation of healthy probiotic bacteria in the lowerdigestive tract, thus helping to fortify the natural digestivedefense system (Welin 2002). By actively colonizing thelower digestive tract, ProBio PCC may be able to dis-courage the development of pathogenic bacteria, yeast,and urinary tract infections. This effect may be due todirect action, modulation of local immunity, modificationsof the intestinal ecosystem or a combination of theseeffects (Marteau 1998).

Clinical Evidence of EfficacyThe primary goal of probiotic therapy is to restore the

natural balance of intestinal microflora in order to havean optimally functioning digestive defense system; thiseffect is well established in published research (FAO/WHO2001). Independent research on probiotics, includingLactobacillus strains, have confirmed the following primaryoutcomes of probiotic therapy: (1) restoration of a healthyintestinal microflora; (2) stimulation of mucosal immunity;(3) improvement in gastrointestinal disturbances, includingfrequency and duration of diarrhea associated with antibi-otics, enteropathogens, and travelers diarrhea; and (4)improvement in urogenital microflora.

Mucosal Immunity

The digestive tract provides a protective interfacebetween our internal environment and a constantly chal-lenging external environment. Approximately 70% of thehuman immune system is localized in the digestive tract(Bengmark 2001). The surface of the intestinal mucosalmembranes is protected by a local adaptive immune sys-tem, characterized by gut-associated lymphoid tissue.This gut-associated lymphoid tissue represents the largestmass of lymphoid tissue in the human body. It has beenproposed that the generation of gut-associated lymphoidtissue and our intestinal immune regulation depends toa large extent on the establishment of indigenous microflora(Isolauri 2001). Probiotic bacteria have been shown to

enhance humoral immune responses and thereby promotethe intestines immunologic barrier. Furthermore, probioticbacteria have been shown to stimulate humoral immuneresponses to enteropathogens, thus aiding in elimination,and to modulate the hosts immune responses to potentiallyharmful antigens (Kaila 1992, Perdigon 1986).

Many probiotic effects are mediated through immuneregulation, by balancing inflammatory substances, normal-izing mucosal function, and maintaining normal intestinalpermeability (Isolauri, 2001, Kalliomaki 2001).

* 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.3 * 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.


5/8

Pre-Clinical StudiesL. fermentum PCCL. fermentum PCC has been shown in animal studies

to have immuno-modulating and anti-fungal activity, whilethe anti-bacterial activity seen in laboratory studies havebeen confirmed in animal model studies for some pathogens.

Pre-clinical studies have shown that L. fermentumPCC is stable and that the strain can survive transitthrough the digestive tract. Colonization of the humandigestive tract has been demonstrated after a single dose;the duration of colonization varied between individualswith a mean value of 14 days (Gibson 1994).

Adhesion and colonization of the human digestivetract has been indicated as a key criterion for selection of pro-biotics. L. fermentum PCC has been shown both in vitroand in vivo to adhere to the human intestinal mucosa. Aninvestigative study in which intestinal mucosal sampleswere treated with PCC-specific antiserum, showed thatL. fermentum PCC was associated with the small intestinalmucosa after oral administration. The investigators proposedthat this attachment could allow prolonged colonizationof the entire tract and contribute to the probiotic effectivenessof this strain. The mucosal attachment could also contributeto the observed immunomodulation observed in otherstudies (Welin 2002). (see graph)

There is emerging evidence that strains of Lactobacillusbacteria that have the capacity to associate with the PeyersPatch (an area of mucosal lymphoid tissue in the smallintestine) have a greater potential to trigger the mucosalimmune system. Researchers have found that L. fermentumPCC preferentially targeted, and was recovered from, thePeyers Patch in mice; hence, L. fermentum PCC could havean enhanced capacity to trigger the mucosal immunesystem (Plant 2002). (see graph)

Clinical StudiesL. fermentum PCCThe health benefits of L. fermentum PCC are documented

in human, animal, and in vitro studies. Twelve clinicalstudies have been completed, or are in progress, validatingthe stability, colonization, and clinical efficacy of L. fer-mentum PCC. Additional clinical studies are currently in

progress. This proprietary strain has been shown in clinicalstudies to prevent the development of diarrhea, and reducethe symptoms of irritable bowel syndrome, includingdiarrhea, constipation, flatulence, bloating, and abdominalpain (Conway 2002, Li 2002). Sixteen animal and in vitrostudies 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 thosereported to date have had limited success with smallimprovements noted. To determine the effects of L. fer-mentum on travelers diarrhea, 300 Swedish soldiers trav-elling to Lebanon were given L. fermentum three days priorto departure and for four weeks on location. In this study,a statistically significant reduction (50%) in the incidenceof gastrointestinal disturbances and diarrhea was noted.Furthermore, those subjects that received the L. fermentumPCC had less severe symptoms than those who receivedL. acidophilus or placebo (Conway 2002). (see graph)

A crossover, single-blind, placebo controlled study wasinitiated to evaluate the effects of L. fermentum on fecalmicrobes and symptoms in patients with Irritable BowelSyndrome (IBS). L. fermentum administered together withresistant starch resulted in an improvement in symptoms

when compared to placebo and baseline results. The fecalmicrobial population was correlated with symptoms andit was shown that the pathogenic bacteria were consistentlyhigh when symptoms were more severe. It is also interestingto note that in laboratory fermentation studies, it has beenshown that these enteric bacteria were reduced when L. fer-mentumwas added to the fermentation vessel, alone or incombination with a high amylose resistant starch (Li 2002).

Proprietary ProcessingThe 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 avail-able in the industry. ProBio PCC has been developedthrough scientific and analytical methods to ensure thatthe product meets label claims for live cultures (CFUs) atthe end of shelf life, which is a more valid indicator ofefficacy than claiming number of live cultures at manu-facturing. Pharmanex has established an exclusive supplyagreement with the supplier of L. fermentum PCC, makingthis unique strain proprietary to our company. L. fermentumPCC is a patent-pending strain of Lactobacillus bacteriawith ten patents having been filed to date. In developing

* 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. 4* 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.


6/8

* 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.

ProBio PCC, Pharmanex has followed the probioticguidelines as established by the FAO/WHO expert con-sultation for pH survival, colonization, identity, anddosing (FAO/WHO 2001).

The ingredients in ProBio PCC have been testedfor purity, and where applicable, ingredients are certifiedpure by testing for unwanted microbes, including Salmonella,E. coli, other coliforms, and Staphylococcus aureus. Additional

tests include total plate counts, yeasts, molds and pesticideresidues. Our manufacturers go through a detailed selectionand certification process to assure their compliance withGood Manufacturing Practice (GMP) standards set by theFood and Drug Administration (FDA).

Side EffectsThere are no known side effects at the recommended

dosage.

Safety and ToxicityProBio PCC is safe and well tolerated at the recom-

mended dosage. Lactobacilli have a long history of use asprobiotics without established risk to humans, whichremains the best proof of safety (Naidu 1999, FAO/WHO2001). Also no pathogenic or virulent properties havebeen found (Aguirre 1993). Probiotics containingLactobacillus have been shown to be safe in children(FAO/WHO 2001).

Contraindications/Drug InteractionsIf you are pregnant or lactating, or taking a prescription

medication, consult a physician prior to use. There are noknown drug interactions, with the exception of antibioticsas mentioned above.

Directions for UseProBio PCC is recommended for adults who expe-

rience occasional diarrhea, constipation, or cramps as aresult of distressed digestive flora, and for adults whoexperience occasional gastrointestinal disturbances suchas gas or bloating. Take one capsule daily to maintainnormal digestive health. While L. fermentum has beenshown to actively colonize the lower digestive tract, con-tinuous ingestion it is recommended for best results.

How SuppliedProBio PCC is supplied in a 30 day supply of

30 capsules.

StorageStore in a cool, dry place. Avoid excessive heat. Protect

from light. This product does not require refrigeration.

Shelf LifeExpiration date and lot code numbers are stamped

on the bottle.

WarningsKeep out of reach of children. If you are pregnant

or nursing, or taking a prescription medication, consulta physician before using this product.

References1. 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. AntimicrobAgents Chemother 1997;41:104652.

8. Conway PL, Blomberg L. Reduction in incidence andseverity of diarrhoea in soldiers consuming Lactobacillusfermentum 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 organ-ism from human faeces after oral dosing. In HumanHealth: The contribution of microorganisms in SpringerSeries 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 andprobiotics. 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 foodincluding powder milk with live lactic acid bacteria.Crdoba, Argentina. October 14, 2001.

20. Kaila M, et al. Enhancement of the circulating antibodysecreting cell response in human diarrhea by a human lac-tobacillus 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 Immunol1997;99:17986.

25. Marteau P, Rambaud JC. Probiotiques en gastroenerologie:bases rationelles, effet demontres et perspectives. Hepato-Gastro 1998;5:267273.

26. Marteau PR, et al. Protection from gastrointestinal disease withthe use of probiotics. Am J Clin Nutr 2001;73(suppl):430S6S.

27. Metchnikoff E. Lactic acid as inhibiting intestinal putrefac-tion. In The prolongation of life: optimistic studies. W.Heinemann, London, pg. 161183. 1907.

* 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.5


7/8

* 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.

28. Mitsuoka T. Intestinal flora and ageing. Nutr Rev1992;50:43846.

29. Naidu AS, Biblack WR, Clemens RA. Probiotic spectra oflactic acid bacteria (LAB). Crit Revs Food Sci & Nutr1999;(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 tointestinal mucus. Int Dairy J 1999;9:62330.

32. Perdigon G, et al. Effect of perorally administered lacto-bacilli on macrophage activation in mice. Infect Immun1986;53:40410.

33. Plant L, Conway PL. Association of Lactobacillus spp withPeyers Patches in mice. Clinical and DiagnosticImmunology 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, andsynbiotics approaching a definition. Am J Clin Nutr2001;73(suppl):361S4S.

37. Shanahan F. Inflamm Bowel Dis 2000;6:10715.38. Tannock GW. Analysis of the intestinal microflora: A

renaissance. Antonie van Leenwenhoek1999;76:265278.

39. Welin A, Farthing M, Conway PL. Publication in prepara-tion (in file), 2002.

6


8/8

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

1998 Pharmanex. All Rights Reserved.

75 West Center Provo, Utah 84601

Tel: 1-801-345-9800 Fax: 1-800-800-0259

www.pharmanex.com01 101093/1

The Pharmanex 6S Quality ProcessCentral to the Pharmanex mission of transforming time-honored, tradition-

al preparations into health promoting botanical products with known con-

tent and consistent activity is the Pharmanex 6S Quality Process.

Probio PCC

Documents

Transcript of Probio PCC