Objectives. The Uses and Dangers of Probiotics 9/23/2014

Transcription

1 The Uses and Dangers of Probiotics Megan Koyle, Pharm.D. Anthony Nelson, Pharm.D. PGY1 residents Boise VAMC Objectives Describe and define probiotics List common products on the market Review possible mechanisms of action that may be beneficial Identify common uses and briefly discuss current evidence Identify less common uses and briefly discuss current evidence (or lack there of) Recognize potential dangers of probiotic use 1

2 PRO-BIO-TIC 1 Pro: derived from Greek, meaning promoting or for Bio: life tic: pertaining to QUIZ TIME! 2 Who was the FATHER of probiotics? A. Louis Pasteur B. Al Gore C. Elie Metchnikoff D. Hippocrates E. William Proctor 2

3 The FATHER of Probiotics 2 A Russian scientist Proposed theory that toxic bacteria in the gut were a cause of aging Drank rotten milk (lactic acid) to kill these harmful bacteria Wrote a book, that led to the future development of probiotics PRO-BIO-TIC 4 AKA Normal flora Good bacteria Helpful bacteria Friendly bacteria Individual bacteria identified by: Genus Species Strand (number) ( 3

4 Your Normal Flora 4 Contains around 400 strains of bacteria, fungi, and parasites TRILLIONS of bacteria live in our digestive tracts Common bacteria found in supplements: Lactobacillus species Bifidobacteria species Saccaromyces boulardii Products available 4 Over 100 products are commercially available 4

5 Examples: Florajen Proviva Culturelle Align Bacid Activia Florastor ( There is NOT generic equivalence with probiotic strains/products due to variability Products have different: Manufacturing methods Storage requirements Species related differences 5

6 ( Try to stick with specific products that have shown benefit in CLINICAL STUDIES Possible Mechanisms ( 6

7 Common Uses 1 Irritable Bowel Syndrome Infectious Diarrhea Antibiotic-Related Diarrhea Traveler s Diarrhea Less Common Uses Allergies Immunity Dental health Cancer prevention Genitourinary health Antihyperlipidemia 7

8 Rumor Has It Rumor vs Truth Probiotics can lower your cholesterol 8

9 Conflicting 5 Studies have shown modest reductions in Total cholesterol and LDL while other have shown no effect Meta- analysis found overall decreases of total (-6.40 mg/dl) and LDL cholesterol (-4.90 mg/dl) Inhibit intestinal cholesterol absorption Occurs through binding of and incorporation of cholesterol in bacterial cells Suppress reabsorption of bile acids Synthesized by cholesterol Rumor vs Truth Probiotics are effective in newborns with intestinal infections 9

10 YES! But 6 This has only been studied in preterm infants There has been some evidence showing the use of probiotics in infant prevents necrotizing enterocolitis NEC may be due to abnormal bacterial colonization Dicloflor Culturelle Florastor Infloran Bifidobacterium A number of commercial product infant mild formulas contain probiotics Rumor vs Truth Probiotics are recommended for antibioticassociated diarrhea 10

11 *TRUTH 7 Several meta-analysis have showed reductions in risk for development of antibiotic associated diarrhea (AAD) Results: Relative risk reduction of 32% Number needed to treat: 13 Consistent across subgroup analysis Other sources say approximately 60-65% reduction in AAD incidence (cite source)-see refere Most commonly studied species included: Lactobacillus, Saccaromyces boulardii, and bifidobacterium RECENT NEWS PLACIDE study Conducted in Wales and northeastern England Involved 5 hospitals, 68 different medical and surgical units, and more than 17,000 patients aged 65 years or older. Showed no benefit, with increased risk for flatulence and bloating 11

12 How much, how long??? 6 Lactobacillus or Bifidobacterium spp: Most studies conducted with 3-5 billion CFU/day BID Saccaromyces boulardii: 500 mg BID if standardized to (30 billion/g) Should try to use formulations/species that were used in clinical trials Rumor vs Truth Probiotics reduce your risk of cancer 12

13 Maybe β-glucuronidase : Produced by pathogenic bacteria in the GI tract levels increase tumor growth production of blood vessels that feed the tumor Convert certain molecules into procarcinogens Colon cancer Bladder cancer Breast cancer Rumor vs Truth Probiotics can prevent travelers-diarrhea 13

14 Possibly 8,9 Mixed results Meta-analysis in 2007 showed a 15% relative risk reduction for traveler s diarrhea Saccaromyces boulardii and mixture of lactobacillus and bifidobacterium showed most benefit Rumor vs Truth Probiotics can help decrease risk of developing allergies 14

15 It s Promising! 18 Ureaplasma urealyticum Colonize the human genital tract women taking probiotics during pregnancy in the incidence of childhood eczema in infants May show some positive evidence for ashtma L. rhamnosus GG Rumor vs Truth Probiotics can be used to prevent Lung infections 15

16 YES! Several clinical trials have evaluated probiotics for preventing respiratory tract infections Common cold Sinusitis Pharyngitis Acute otitis media Rumor vs Truth Probiotics can be used to treat and prevent irritable bowel syndrome 16

17 Perhaps yes, perhaps not 10 Conflicting evidence May decrease symptoms of Irritable Bowel Syndrome-Constipation abdominal discomfort bloating difficult bowel movements Primarily evidence for Bifidobacterium Rumor vs Truth Probiotic promote female reproductive and bladder health 17

18 Yes and No May be helpful in bacterial vaginosis Lactobacilli produce hydrogen peroxide and lactic acid which lower vaginal ph and may help prevent the overgrowth of other bacteria A number of studies have failed to demonstrate protection UTIs Yeast infections Does not seem to reduce the risk of vaginal candidiasis infection following use of antibiotics Rumor vs Truth Probiotics prevent tooth decay 18

19 YES! But 11,12 Systemic review of 23 randomized clinical trials assesing use of probiotics on oral health In two-thirds of the selected papers, probiotics demonstrated a capacity to reduce S. Mutans counts in saliva and/or plaque. But to date, RCTs on this topic are insufficient to provide scientific clinical evidence. Probiotics and oral protection 11,12 Has been shown to prevent Dental caries Periodontitis Oral fungal infections Halitosis 19

20 Probiotics and Teeth 11,12 Probiotics may inhibit bacteria S. Mutans from forming biofilms in our mouths Preventing adhesion of bacteria Competing for nutrients Enhance immune responses Rumor vs Truth Probiotics can treat and prevent infectious-diarrhea 20

21 TRUTH! May duration of infectious diarrhea by 30.5 hours Primarily due to Rotovirus Theoretical Dangers of Probiotics 15,16 Ability to cause infection Transfer of antibiotic resistance to the GI flora Toxic effects to the GI tract 21

22 Dangers of Probiotics 15,16 Risk of bacteremia & fungemia Bifidobacterium Endocarditis Lactobacilli Species Sepsis endocarditis Saccharomyces boulardii Fungemia Proposed Risk Factors for Probiotic Bacteremia/Fungemia 15,16 Major risk factors 1) Immune compromise, including a debilitated state or malignancy 2) Premature infants Minor risk factors 1) Central venous catheters 2) Impaired intestinal epithelial barrier, eg, diarrheal illness, intestinal inflammation 3) Administration of probiotic by jejunostomy 4) Concomitant administration of broad spectrum antibiotics to which probiotic is resistant 5) Probiotics with properties of high mucosal adhesion or known pathogenicity 6) Cardiac valvular disease (Lactobacillus probiotics only) 22

23 Dangers of Probiotics Lactobacillus species Contain plasmids for antibiotic resistance Tetracyclines Erythromycin Chloramphenicol Transfer to other bacteria is rare Dangers of Probiotics 15,16 Potential risk of GI toxicity GI tract breaking down lactic acid bacteria Lactic acidosis Probiotics prevent deconjugation of bile salts Malabsorption 23

24 When Choosing a probiotic 17 Check the label Beware of the internet Pick certified probiotics Storage Finally Scientific evidence supporting specific uses is still lacking The FDA has not approved any health claims Probiotics do not replace any proven treatments Monitor closely if any serious underlying health problems 24

25 Summary Probiotics have many potential uses There are vast amounts of information about probiotics and much of this information is conflicting It is important is to weigh the potential risks and benefits based on individual patient factors References 1. Pharmacist letter. Online Training Course Probiotics. Accessed August 10, =13-103&pm=0&quiz=1#references 2. Wikipedia. Élie Metchnikoff. August 10, Saljoughian, M. Probiotics: a Closer Look. Accessed August 10, Guo Zhuang et al. Research advances with regards to clinical outcome and potential mechanisms of cholesterol-lowering effects of probiotics. Clinical Lipidology. 2012; NCCAM. Oral Probiotics: An Introduction. Accessed August 10, Hempel S, Newberry SJ, Maher AR, et al. Probiotics for the prevention and treatment of antibioticassociated diarrhea: a systematic review and meta-analysis. JAMA May 9;307(18): doi: /jama D'Souza AL, Rajkumar C, Cooke J, Bulpitt CJ. Probiotics in prevention of antibiotic associated diarrhea: meta-analysis. BMJ 2002;324: Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev. 2004;(2):CD Review. Update in: Cochrane Database Syst Rev. 2010;(11) 25

26 References 10. Goldin BR et.al.clinical Indications for Probiotics: An Overview. Clin Infect Dis. (2008) 46 (Supplement 2): S96-S Cagetti MG, Mastroberardino S, Milia E, Cocco F, Lingström P, Campus G. The use of probiotic strains in caries prevention: a systematic review. Nutrients Jul 5;5(7): Bizzini B, Pizzo G, Scapagnini G, Nuzzo D, Vasto S. Probiotics and oral health. Curr Pharm Des. 2012;18(34): Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101: McFarland LV. Meta-analysis of probiotics for the prevention of traveler's diarrhea. Travel Med Infect Dis Mar;5(2): Snydman DR. The safety of probiotics. Clin Infect Dis Feb 1;46 Suppl 2:S104-11; discussion S Boyle RJ, et. al.probiotic use in clinical practice: What are the risks? Am J Clin Nutr June 2006 vol. 83 no Probiotics: What they are and what they can do for you. American Gastroenterological Association. Accessed July 20, Goldin BR et.al.clinical Indications for Probiotics: An Overview. Clin Infect Dis. (2008) 46 (Supplement 2): S96-S