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TRANSCRIPT
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The Uses and Dangers of ProbioticsMegan 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
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PRO-BIO-TIC1 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
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The FATHER of Probiotics2 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-TIC4 AKA
Normal flora
Good bacteria
Helpful bacteria
Friendly bacteria
Individual bacteria identified by: Genus
Species
Strand (number)
(http://www.dfwchild.com/Fort-Worth/features/1014/Keeping-Kids-Healthy-With-Probiotics)
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Your Normal Flora4 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 available4 Over 100 products are commercially
available
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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
(http://www.mc.vanderbilt.edu/root/vumc.php?site=preceptorprogram&doc=42329)
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Try to stick with specific products that have shown benefit in CLINICAL STUDIES
(http://www.mc.vanderbilt.edu/root/vumc.php?site=preceptorprogram&doc=42329)
Possible Mechanisms
(http://ncp.sagepub.com/content/24/1/10/F1.large.jpg)
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Common Uses1 Irritable Bowel Syndrome
Infectious Diarrhea
Antibiotic-Related Diarrhea
Travelers Diarrhea
Less Common Uses Allergies
Immunity
Dental health
Cancer prevention
Genitourinary health
Antihyperlipidemia
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Rumor Has It
Rumor vs TruthProbiotics can lower your cholesterol
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Conflicting5 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 TruthProbiotics are effective in newborns with intestinal infections
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YES! But6 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 TruthProbiotics are recommended for antibiotic-associated diarrhea
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*TRUTH7 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
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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 TruthProbiotics reduce your risk of cancer
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Maybe -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 TruthProbiotics can prevent travelers-diarrhea
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Possibly8,9 Mixed results
Meta-analysis in 2007 showed a 15% relative risk reduction for travelers diarrhea
Saccaromyces boulardii and mixture of lactobacillus and bifidobacterium showed most benefit
Rumor vs TruthProbiotics can help decrease risk of developing allergies
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Its 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 TruthProbiotics can be used to prevent Lung infections
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YES! Several clinical trials have evaluated
probiotics for preventing respiratory tract infections Common cold
Sinusitis
Pharyngitis
Acute otitis media
Rumor vs TruthProbiotics can be used to treat and prevent irritable bowel syndrome
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Perhaps yes, perhaps not10 Conflicting evidence
May decrease symptoms of Irritable Bowel Syndrome-Constipation abdominal discomfort
bloating
difficult bowel movements
Primarily evidence for Bifidobacterium
Rumor vs TruthProbiotic promote female reproductive and bladder health
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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 TruthProbiotics prevent tooth decay
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YES! But11,12 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 protection11,12 Has been shown to prevent
Dental caries
Periodontitis
Oral fungal infections
Halitosis
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Probiotics and Teeth11,12 Probiotics may inhibit bacteria S. Mutans
from forming biofilms in our mouths
Preventing adhesion of bacteria
Competing for nutrients
Enhance immune responses
Rumor vs TruthProbiotics can treat and prevent infectious-diarrhea
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TRUTH! May duration of
infectious diarrhea by 30.5 hours Primarily due to
Rotovirus
Theoretical Dangers of Probiotics15,16 Ability to cause infection
Transfer of antibiotic resistance to the GI flora
Toxic effects to the GI tract
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Dangers of Probiotics15,16 Risk of bacteremia & fungemia
Bifidobacterium
Endocarditis
Lactobacilli Species Sepsis endocarditis
Saccharomyces boulardii
Fungemia
Proposed Risk Factors for Probiotic Bacteremia/Fungemia15,16
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)
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Dangers of Probiotics Lactobacillus species
Contain plasmids for antibiotic resistance
Tetracyclines Erythromycin Chloramphenicol
Transfer to other bacteria is rare
Dangers of Probiotics15,16 Potential risk of GI toxicity
GI tract breaking down lactic acid bacteria Lactic acidosis
Probiotics prevent deconjugation of bile salts Malabsorption
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When Choosing a probiotic17 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
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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
References1. Pharmacist letter. Online Training Course Probiotics. Accessed August 10, 2014.
http://pharmacistsletter.therapeuticresearch.com/ce/ceCourse.aspx?rn=2&cs=student&s=PL&pc=13-103&pm=0&quiz=1#references
2. Wikipedia. lie Metchnikoff. http://en.wikipedia.org/wiki/%C3%89lie_Metchnikoff .Accessed August 10, 2014
3. http://patients.gi.org/topics/probiotics-for-the-treatment-of-adult-gastrointestinal-disorders/
4. Saljoughian, M. Probiotics: a Closer Look. Accessed August 10, 2014. http://www.uspharmacist.com/content/c/9786/?t=men's_health,gastroenterology
5. Guo Zhuang et al. Research advances with regards to clinical outcome and potential mechanisms of cholesterol-lowering effects of probiotics. Clinical Lipidology. 2012;501-507.
6. NCCAM. Oral Probiotics: An Introduction. Accessed August 10, 2014. http://nccam.nih.gov/health/probiotics/introduction.htm
7. Hempel S, Newberry SJ, Maher AR, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012 May 9;307(18):1959-69. doi: 10.1001/jama.2012.3507.
8. D'Souza AL, Rajkumar C, Cooke J, Bulpitt CJ. Probiotics in prevention of antibiotic associated diarrhea: meta-analysis. BMJ 2002;324:1361
9. Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev. 2004;(2):CD003048. Review. Update in: Cochrane Database SystRev. 2010;(11)
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References
10. Goldin BR et.al.Clinical Indications for Probiotics: An Overview. Clin Infect Dis. (2008) 46 (Supplement 2): S96-S100.
11. Cagetti MG, Mastroberardino S, Milia E, Cocco F, Lingstrm P, Campus G. The use of probiotic strains in caries prevention: a systematic review. Nutrients. 2013 Jul 5;5(7):2530-50.
12. Bizzini B, Pizzo G, Scapagnini G, Nuzzo D, Vasto S. Probiotics and oral health. Curr Pharm Des. 2012;18(34):5522-31.
13. Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101:15811590.
14. McFarland LV. Meta-analysis of probiotics for the prevention of traveler's diarrhea. Travel Med Infect Dis. 2007 Mar;5(2):97-105.
15. Snydman DR. The safety of probiotics. Clin Infect Dis. 2008 Feb 1;46 Suppl 2:S104-11; discussion S144-51.16. Boyle RJ, et. al.Probiotic use in clinical practice: What are the risks? Am J Clin Nutr June 2006 vol. 83
no. 6 1256-1264
17. Probiotics: What they are and what they can do for you. American Gastroenterological Association. Accessed July 20, 2014. http://www.gastro.org/patient-center/diet-medications/probiotics
18. Goldin BR et.al.Clinical Indications for Probiotics: An Overview. Clin Infect Dis. (2008) 46 (Supplement 2): S96-S100.