Advanced probiotic strategies for exceptional patient outcomes

1. Advanced probiotic strategies for exceptional patient outcomes

2. GI microbial imbalance has been associated with: • Antibiotic Associated Diarrhea • Travelers Diarrhea • Gastritis • Irritable Bowel Syndrome (IBS) • Inflammatory Bowel Disease (IBD) and Crohn’s Disease • Food Allergy • Psoriasis, Eczema, Cystic Acne • Functional Dyspepsia • Ulcer • Autoimmune Disease • Chronic Yeast Infections Your patients’ health begins with the health of their GI microflora • Approximately 70% of your patients’ immune system is found in the GI tract

3. Specific strains of probiotic bacteria have demonstrated clinical benefit • Promotes normal intestinal functions and may help reduce constipation • Helps to reduce harmful bacteria and stimulates improved immune function • May help control urogenital infections • Improves the digestion of lactose • Beneficial for irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) • Helps to protects against infection by pathogens including yeast • Decreases side effects of antibiotic therapy such as diarrhea

4. Only a handful of probiotic strains are responsible for the lions share of the clinical research. Some of these include: L. plantarum 299V L. acidophilus NCFM S. boulardii

5. Genus, Species and Strain Characterization Although many strains are commercially available, very few have supporting clinical data

6. Each strain has an effect on various cytokines within the body Depending on their effect on enteric cells, different probiotic strains may influence inflammation, allergy and immune response

7. Research on specific strains does not transfer to other strains within that species Importance of Strain “…it has been clearly demonstrated that probiotic properties are strain-specific and cannot be extrapolated to other strains.” (Best Pract Res Clin Gastroenterol. 2003 Oct;17(5))

8. L. acidophilus NCFM Great for IBS L. plantarum 299V Great for inflammation L. rhamnosus HN001 Boosts immunity When choosing a probiotic rely on the specific research around the specific strain to achieve the desired outcome Same species, different function Sled dog - cold-hardy - good endurance - tough feet Guard dog - protective - muscular - strong teeth - ferocious bark - courageous Hunting dog - soft mouth - good swimmer All dogs not ideal for all purposes

9. What to look for in a clinically relevant probiotic… Research ? Potency ? Stability ?

10. When choosing a formula, look to the research on the primary strain (S. boulardii ) (L. acidophilus NCFM) (L. plantarum 299V) Hundreds of human clinical studies in varied patient populations result in exceptional patient outcomes

11. For improved outcomes, compliment the primary strains with additional well-researched condition-specific strains • Immune support • Combine S. boulardii with: • B. lactis HN019 • L. rhamnosus HN001 • Well rounded GI support • Combine L. acidophilus NCFM with: • B. lactis BI-07

12. Choose potency at levels supported by published research • S. boulardii / L. rhamnosus HN001 / B. lactis HN019 • 5.5 billion cfu + 4 billion cfu • L. acidophilus NCFM / B. lactis BI-07 • 60 billion cfu • L. plantarum 299V • 18 billion cfu Often commercial probiotic brands offer lower potency to meet price points cfu = colony forming unit

13. 37 Low potency formulas may result in poor clinical results or compliance and cost challenges with your patients L. acidophilus NCFM / B. lactis BI-07 Typical retail probiotic 15 billion cfu 3 billion cfu

14. Look for stability and expiration guarantees • Stable at room temperature • Multiple assays ensure product quality • Guaranteed label claim at time of expiration

15. Temperature stability ensures potency over time

16. For many manufacturers, stability at room temperature is a significant challenge

17. Often manufacturers claim that they have stability, but instead put in high overages to meet label claim 43% loss 57% loss

18. Many other manufacturers just state that the product met label claim at time of manufacture ? ? ? ?

19. Ensure that your probiotics are shipped refrigerated to be delivered pristine Shipping temperatures may accelerate die off

20. Be sure that the strain is genetically verified with periodic DNA testing

21. Confirm that each lot is tested for resistance to acid and bile to ensure that it is strong enough to survive

22. Ensure quality with assays at multiple production steps Bulk material Bile resistance Label claim Final analytical

23. Guidelines for selecting probiotics that offer the greatest benefit

26. For which conditions would you typically recommend strain-specific probiotics in your practice

27. Overall GI health Cold and flu and post antibiotic therapy Irritable Bowel Syndrome (IBS) Inflammation & IBD

28. A fantastic choice for overall GI health L. acidophilus NCFM / B. lactis BI-07 • Published studies showing positive effects: • Improved lactose digestion • Cholesterol Lowering • Immune balancing • Antimicrobial

29. Volumes of supporting data make this a fantastic choice to support overall GI health Published Studies Cytokine Activity Survivability

30. L. acidophilus NCFM is the only probiotic strain that whose DNA has been fully mapped PNAS March 15, 2005 vol. 102 no. 11 3906–3912

31. L. acidophilus NCFM encourages production of lactase enzymes that facilitate milk digestion

32. Recent research indicates that L. acidophilus NCFM / B. lactis BI-07 may reduce the incidence of respiratory infection in children “CONCLUSIONS: Daily consumption of NCFM and Bi-07 and of NCFM alone significantly reduced the incidence and duration of respiratory tract infection symptoms in children.” Pediatrics 2008;121;S115, Arthur Ouwehand, Greg Leyer and Didier Carcano

33. Recommend this well-studied, high quality probiotic • to patients as daily support for GI health • to support and balance GI microflora • to support lactose digestion A great tool to balance and support overall GI health

34. Post antibiotic therapy and immune support S. boulardii / B. lactis HN019 / L. rhamnosus HN001 • S. boulardii has been studied in numerous double blind placebo controlled trials • Indicated for C. difficile after antibiotics • HN019 and HN001 support NK cell activity

35. A great solution for patients before, during and after an immune challenge • Recommend this advanced strategy for patients: • That have recently taken antibiotics • Present with recurrent diarrhea • Have plans to travel abroad • Have immune support concerns

36. Support the your patients’ GI health by prescribing S. boulardii during and after antibiotic therapy • Am J Gastroenterol. 1995 Mar;90(3):439-48 • Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo. • McFarland LV, Surawicz CM, Greenberg RN, Elmer GW, Moyer KA, Melcher SA, Bowen KE, Cox JL. • OBJECTIVES: To determine the safety and efficacy of a new preventive agent for antibiotic-associated diarrhea (AAD) in patients receiving at least one beta-lactam antibiotic. METHODS: A double-blinded, placebo-controlled, parallel group study was performed in a high-risk group of hospitalized patients receiving a new prescription for a beta-lactam antibiotic and having no acute diarrhea on enrollment. Lyophilized Saccharomyces boulardii or placebo (1 g/day) was given within 72 h of the start of the antibiotic(s) and continued until 3 days after the antibiotic was discontinued, after which the patients were followed for 7 wk. RESULTS: Of the 193 eligible patients, significantly fewer, 7/97 (7.2%), patients receiving S. boulardii developed AAD compared with 14/96 (14.6%) on placebo (p = 0.02). The efficacy of S. boulardii for the prevention of AAD was 51%. Using a multivariate model to adjust for two independent risk factors for AAD (age and days of cephalosporin use), the adjusted relative risk was significantly protective for S. boulardii (RR = 0.29, 95% CI = 0.08, 0.98). CONCLUSION: The prophylactic use of S. boulardii given with a beta-lactam antibiotic resulted in a significant reduction of AAD with no serious adverse reactions. “CONCLUSION: The prophylactic use of S. boulardii …resulted in a significant reduction of AAD (antibiotic-associated diarrhea)”

37. S. boulardii is a great tool to help your patients combat harmful microbes Supports the removal pathogenic microbes • Pediatr Nephrol. 2006 Jun;21(6):807-10 • Influence of oral intake of Saccharomyces boulardii on Escherichia coli in enteric flora • Ipek Akil1, 4 , Ozge Yilmaz1, Semra Kurutepe2, Kenan Degerli2 and Salih Kavukcu3 • Abstract  Enteric flora constitutes 95% of the cells in the human body. It has been shown that the bacterial content of this flora is affected by diet and changes in nutrition. Considering that urinary tract infections (UTI) are mostly due to ascending infections from the gut flora, the importance of the elements of this flora and their characteristics becomes more evident. The aim of this study was to evaluate the influence of oral Saccharomyces boulardii (S. boulardii) intake on the number of Escherichia coli (E. coli) colonies in the colon. This study was carried out with 14 boys and 10 girls (total of 24 children) aged between 36 and 192 months (mean: 104.3±45.1 months). A commercial capsule or powder containing 5 billion colony-forming units (cfu) of S. boulardii was administered once a day for 5 days. The number of E. coli and yeast colonies was measured in the stool samples of the study group before and after the use of this drug. Before treatment, the mean number of E. coli colonies in g/ml stool was 384,625±445,744. This number decreased significantly to 6,283±20,283 after treatment (p=0.00). S. boulardii was not detected in stool before treatment and the number of colonies increased to 11,047±26,754 in g/ml stool. S. boulardii may be effective in reducing the number of E. coli colonies in stool. The influence of this finding on clinical practice such as prevention of UTI needs to be clarified by further studies. E. Coli • Am J Gastroenterol. 2006 Apr;101(4):812-22 • Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. • Lynne V. McFarland, Ph.D.1,21 • CONTEXT:  Antibiotic-associated diarrhea (AAD) is a common complication of most antibiotics and Clostridium difficile disease (CDD), which also is incited by antibiotics, is a leading cause of nosocomial outbreaks of diarrhea and colitis. The use of probiotics for these two related diseases remains controversial. OBJECTIVE:  To compare the efficacy of probiotics for the prevention of AAD and the treatment of CDD based on the published randomized, controlled clinical trials. DATA SOURCES:  PubMed, Medline, Google Scholar, NIH registry of clinical trials, metaRegister, and Cochrane Central Register of Controlled Trials were searched from 1977 to 2005, unrestricted by language. Secondary searches of reference lists, authors, reviews, commentaries, associated diseases, books, and meeting abstracts. STUDY SELECTION:  Trials were included in which specific probiotics given to either prevent or treat the diseases of interest. Trials were required to be randomized, controlled, blinded efficacy trials in humans published in peer-reviewed journals. Trials that were excluded were pre-clinical, safety, Phase 1 studies in volunteers, reviews, duplicate reports, trials of unspecified probiotics, trials of prebiotics, not the disease being studied, or inconsistent outcome measures. Thirty-one of 180 screened studies (totally 3,164 subjects) met the inclusion and exclusion criteria. DATA EXTRACTION:  One reviewer identified studies and abstracted data on sample size, population characteristics, treatments, and outcomes.DATA SYNTHESIS:  From 25 randomized controlled trials (RCTs), probiotics significantly reduced the relative risk of AAD (RR = 0.43, 95% CI 0.31, 0.58, p < 0.001). From six randomized trials, probiotics had significant efficacy for CDD (RR = 0.59, 95% CI 0.41, 0.85, p= 0.005).CONCLUSION:  A variety of different types of probiotics show promise as effective therapies for these two diseases. Using meta-analyses, three types of probiotics (Saccharomyces boulardii Lactobacillus rhamnosus GG, and probiotic mixtures) significantly reduced the development of antibiotic-associated diarrhea. Only S. boulardii was effective for CDD. C. Difficile • J Infect Dis. 1993 Nov;168(5):1314-8. • Inhibition of Candida albicans translocation from the gastrointestinal tract of mice by oral administration of Saccharomyces boulardii.Berg R, Bernasconi P, Fowler D, Gautreaux M.Dept. of Microbiology and Immunology, Louisiana State University Medical Center, Shreveport 71130.Microbial translocation is defined as the passage of viable microbes from the gastrointestinal (GI) tract to extraintestinal sites, such as the mesenteric lymph node (MLN), spleen, liver, kidneys, and blood. The ability of orally administered viable Saccharomyces boulardii to inhibit Candida albicans translocation from the GI tract was tested in antibiotic-decontaminated, specific pathogen-free (SPF) mice, which were orally challenged with C. albicans to promote intestinal overgrowth and subsequent translocation of this organism. Oral S. boulardii treatment reduced the incidence of MLN cultures positive for C. albicans but did not decrease the numbers of C. albicans per gram of MLN in these immunocompetent mice. Prednisolone immunosuppression increased translocation of C. albicans to the MLN and allowed translocating C. albicans to spread systemically to the spleen, liver, and kidneys. In these immunosuppressed mice, orally administered S. boulardii decreased both the incidence of C. albicans translocation to the MLN, liver, and kidneys and the number of translocating C. albicans per gram of MLN, spleen, and kidneys. Candida albicans • Pakistan Journal of Biological Sciences 9 (4): 632-635, 2006 • The Preventive Effect of Sacharomyces boulardii in Pathogenesis of Salmonella typhimurium in Experimentally Infected Rats • M. Mahzounieh, I. Karimi, T. Zahraei Salehi and R. Marjanian • The present research studied the capacity of Saccharomyces boulardii (S. boulardii) to antagonize Salmonella typhimurium (S. typhimurium) in the intestinal tract and humoral response of rats after challenging with S. typhimurium. Sixty conventional male rats were divided at random into 4 groups. The S.boulardii suspensions contained 106, 07 and 108 cells mL-1 were administered (orally) to 3 groups (A, B and C) of rats, respectively for 5 continues days. The rats of group D received Saline instead of S.boulardii and used as control. All of rats challenged with 107 CFU of pathogenic S. typhimurium at fifth day. The viable Salmonella were counted at g-1 of faeces of rates at 0, , 3, 5 and 7 days after challenge. Titer of anti- salmonella antibodies were determined. Present experiments showed that S. boulardii could reduce the bacterial colonization in experimental animals. There was a significant reduction at number of S. typhimurium between control and test groups. A daily dose of 106 yeast cells was resulted in the most reduction in bacterial shedding and high titers of anti salmonella antibodies. The mortality rates were 0 and 46.4% in yeast treatment and control animals, respectively. S. typhimurium viable cells were not detected in the organs of yeast-treated rats. We conclude that S. boulardii has a preventive effect in pathogenesis of S. typhimurium. Salmonella

38. A well accepted approach to manage GI concerns in a variety of patients • Aliment Pharmacol Ther. 2007 Feb 1;25(3):257-64 • Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children. • Szajewska H, Skórka A, Dylag M. • The Second Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland. BACKGROUND: Saccharomyces boulardii is a non-pathogenic probiotic yeast considered useful against enteropathogens. AIM: To assess the effectiveness of S. boulardii in treating acute infectious diarrhoea in children. METHODS: The following electronic databases were searched through August 2006 for studies relevant to acute infectious diarrhoea and S. boulardii: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials were included. RESULTS: Five randomized-controlled trials (619 participants) met the inclusion criteria. Combined data from four randomized-controlled trials showed that S. boulardii significantly reduced the duration of diarrhoea compared with control. The pooled weighted mean difference was -1.1 days (95% CI: -1.3 to -0.8) with a fixed model and remained significant in a random effect model. Saccharomyces boulardii significantly reduced the risk of diarrhoea on days 3, 6 and 7. Also the risk of diarrhoea lasting >7 days was significantly reduced in the S. boulardii group vs. control group (1 RCT, n = 88, RR 0.25, 95% CI: 0.08-0.83; NNT 5, 95% CI: 3-20). CONCLUSIONS: There exists a moderate clinical benefit of S. boulardii therapy in otherwise healthy infants and children with acute gastroenteritis, mainly a shorter duration of diarrhoea. However, these results should be interpreted with caution due to methodological limitations of the included studies. Intensive Care Medicine Volume 23, Number 5 / May, 1997 Saccharomyces boulardii prevents diarrhea in critically ill tube-fed patients, A multicenter, randomized, double-blind placebo-controlled trial G. Bleichner1, H. Bléhaut2, H. Mentec1, D. Moyse3 Objective: To assess the preventive effect of Saccharomyces boulardii on diarrhea in critically ill tube-fed patients and to evaluate risk factors for diarrhea. Design: Prospective, multicenter, randomized, double-blind placebo-controlled study. Setting: Eleven intensive care units in teaching and general hospitals. Patients: Critically ill patients whose need for enteral nutrition was expected to exceed 6 days. Intervention: S. boulardii 500 mg four times a day versus placebo. Measurements and results: Diarrhea was defined by a semiquantitative score based on the volume and consistency of stools. A total of 128 patients were studied, 64 in each group. Treatment with S. boulardii reduced the mean percentage of days with diarrhea per feeding days from 18.9 to 14.2 % [odds ratio (OR) = 0.67, 95 % confidence interval (CI) = 0.50-0.90, P = 0.0069]. In the control group, nine risk factors were significantly associated with diarrhea: nonsterile administration of nutrients in open containers, previous suspension of oral feeding, malnutrition, hypoalbuminemia, sepsis syndrome, multiple organ failure, presence of an infection site, fever or hypothermia, and use of antibiotics. Five independent factors were associated with diarrhea in a multivariate analysis: fever or hypothermia, malnutrition, hypoalbuminemia, previous suspension of oral feeding, and presence of an infection site. After adjustment for these factors, the preventive effect of S. boulardii on diarrhea was even more significant (OR = 0.61, 95 % CI = 0.44-0.84, P < 0.0023). Conclusion: S. boulardii prevents diarrhea in critically ill tube-fed patients, especially in patients with risk factors for diarrhea. Numerous randomized double-blind placebo controlled trials in varied patient populations make S. boulardii a great therapeutic choice for practitioners

39. Two additional probiotic strains to support your patients’ immune systems • J Clin Immunol. 2001 Jul;21(4):264-71. • Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes. • Gill HS, Rutherfurd KJ, Cross ML. • Many elderly subjects are at increased risk of infectious and noninfectious diseases due to an age-related decline in lymphoid cell activity (immunosenescence). Noninvasive means of enhancing cellular immunity are therefore desirable in the elderly. Previous reports have suggested that dietary supplementation could represent an effective means of enhancing the activity of circulating natural killer (NK) cells in the elderly. In the present study, we have conducted a pre-post intervention trial to determine the impact of dietary supplementation with probiotic lactic acid bacteria (LAB) on peripheral blood NK cell activity in healthy elderly subjects. Twenty-seven volunteers consumed low-fat/low-lactose milk supplemented with known immunostimulatory LAB strains (Lactobacillus rhamnosus HN001 or Bifidobacterium lactis HN019) for a period of 3 weeks. A dietary run-in of milk alone was shown to have no significant effect on NK cells. In contrast, the proportion of CD56-positive lymphocytes in peripheral circulation was higher following consumption of either LAB strain, and ex vivo PBMC tumoricidal activity against K562 cells was also increased. Supplementation with HN001 or HN019 increased tumoricidal activity by an average of 101 and 62%, respectively; these increases were significantly correlated with age, with subjects older than 70 years experiencing significantly greater improvements than those under 70 years. These results demonstrate that dietary consumption of probiotic LAB in a milk-based diet may offer benefit to elderly consumers to combat some of the deleterious effects of immunosenescence on cellular immunity. “Supplementation with (L. rhamnosus) HN001 or (B. lactis ) HN019 increased tumoricidal activity by an average of 101 and 62%, respectively”

40. Powerful B. lactis HN019 for demonstrated support for immune function “Consumption of B. lactis HN019 led to average increases in cellular immune function of between 14.5% and 61.8%, with the greatest effect on NK cell activity” “B. lactis HN019 may therefore offer the most promise as a dietary supplement for optimizing or restoring effective immunity” Am J Clin Nutr 2001;74:833–9. American Society for Clinical Nutrition

41. Revolutionary L. rhamnosus HN001 for additional immune support “It is therefore possible that enhanced performance by these cells, following consumption of HN001, could lead to an increased ability of consumers to fight infectious diseases” “Of the immune responses that were enhanced by dietary consumption of HN001, phagocytic activity by PMN (polymorphonuclear) cells constitutes an important anti-microbial defense mechanism … while NK cell killing activity is thought to be important in the control of viral-infected cells.” J Am Coll Nutr. 2001 Apr;20(2 Suppl):149-56.

42. Additional considerations during cold and flu season • Vitamin C complex • A buffered combination of ascorbates and vitamin C metabolites for superior bioavailability Combine: • Bioavailable Vitamin C • Immune-enhancing mushrooms • Immune supporting Zinc

43. Bioavailable Vitamin C complex superior for boosting the body’s natural defenses • 18% to 25% increased uptake in white blood cells • NK activity in Vitamin C complex patients increased between 200-400%* • NK activity in ascorbic acid patients initially decreased where Vitamin C complex patients did not* *Vojdani A, Namatalla G.Enhancement of human natural killer cytotoxic activity by vitamin C in pure and augmented formulations. J Nutr Env Med 1997;7:187-95.

44. Published Research Demonstrates Superiority of Vitamin C complex *J Nutr Env Med 1997;7:187-95 Enhancement of human natural killer cytotoxic activity by vitamin C in pure and augmented formulations A Vojdani, G Namatalla The antitumor activity of ascorbic acid has been reported by different investigators. In this study, we determined the in vivo effects of ascorbic acid and its modified formulation (Ultra Potent-C) on human natural killer (NK) cell activity. Twenty-two healthy subjects were given either ascorbic acid or Ultra Potent-C orally at a concentration of 60 mg kg[-1]. Vitamin C uptake was measured in the plasma and by peripheral blood lymphocytes (PBLs). The uptake of vitamin C by PBLs was maximized at 2-4 h and was maintained at a high level up to 24 h. At the maximal point the uptake of Ultra Potent-C was higher by 18-25% than plain ascorbic acid. In addition, PBL-NK activity was measured by a 4-h [51]Cr release assay using K562 as targets. The results demonstrated that ascorbic acid has a biphasic pattern of NK function; an early transient depression in NK activity (29%) at 1-4 h that is subsequently followed by a significant enhancement (200-400%) between 8 and 24 hours. However, the pattern of NK activity in the Ultra Potent-C group was different from the ascorbic acid group and the early transient depression in NK activity was not observed. We conclude that ascorbic acid or its modified form is a potent immunomodulator • **Immunopharmacol Immunotoxicol. 1997 Aug;19(3):291-312 • Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: • A Vojdani, G Heuser • After exposure to many toxic chemicals, NK function can be decreased significantly. Weeks or months later, natural killer (NK) function can rebound to normal levels in some and can be suppressed for prolonged periods of time in other patients. In view of this, we decided to study the effect of buffered vitamin C on NK, T and B cell function in patients who had been exposed to toxic chemicals. After the first blood draw, 55 patients immediately ingested granulated buffered vitamin C in water at a dosage of 60 mg/Kg body weight. Exactly 24 hours later, blood was again drawn for a follow-up study of NK, T and B cell function. • Vitamin C in high oral dose was capable of enhancing NK activity up to ten-fold in 78% of patients.Lymphocyte blastogenic responses to T and B cell mitogens were restored to the normal level after vitamin C usage. Signal transduction enzyme protein kinase C (PKC) appeared to be involved in the mechanism of induction of NK activity by vitamin C. • We conclude that immune functional abnormalities can be restored after toxic chemical exposure by oral usage of vitamin C. • This study looked at chemically exposed patients with decreased NK activity and T & B cell function • Patients received approximately 3 grams of Vitamin C complex • 78% of patients experienced a 10-fold increase in NK activity** • T and B cell activities were restored to normal levels**

45. Immune-enhancing mushroom extract water extracts of shiitaki, reishi, maitaki, fu-ling, cordyceps, turkey tail and oyster mushrooms, traditionally and scientifically shown to support immune function. The responsible bioactive compounds in these mushrooms belong to several chemical groups, very often water soluble polysaccharides or triterpenes. One species can possess a high variety of compounds resulting in multidimensional effects. Lindequist U et al eCAM 2005; 2(3)285-299

46. For patient with Irritable Bowel Syndrome L. acidophilus NCFM / B. lactis BI-07 • May modulate intestinal pain • May Reduce duration of diarrhea • Supports the GI barrier • 60 billion cfu daily

47. Recommend this high-potency combination for patients presenting with symptoms of IBS: • Frequent urges with constipation or diarrhea • Abdominal discomfort • Bloating and cramping

48. A great tool to address the pain and discomfort of IBS “The similar efficacy, in treating pain, of orally administered L. acidophilus NCFM and a standard dosage of morphine suggests that specific modulation of intestinal flora may be a promising, safe and relatively inexpensive new treatment for abdominal pain, a prominent symptom of irritable bowel syndrome” Nat Med. 2007 Jan;13(1):35-7. Epub 2006 Dec 10

49. L. Acidophilus NCFM and B. lactis BI-07 to address symptoms of IBS Results of Clinical Work Subjects and Methods • 26 IBS patients (23 females; 3 males) • L. Acidophilus NCFM + Bifidobacteria complex • 30 billion live cells two times daily Outcome • IBS-QOL – 63.3 at baseline; after treatment 84.5 indicating significant improved quality of life (p<.001) • SFI – 38.4 at baseline; after treatment, a decrease of 18.7 (p<.001) suggesting significant symptomatic improvement

50. For inflammation and IBD L. Plantarum 299V • Numerous human clinical studies in multiple patient populations • Research in inflammatory conditions such as Ulcerative Colitis • May have an effect on systemic inflammatory markers and cytokines