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Homeopathic Products
• Principle of analogy or Law of Similars
• Small or infinitesimal doses (3X-30C)– Avogadro’s number=6x1023 = ~23X
• Succussion and potentization (seehttp://www.boiron.com/en/htm/02_medi_homeo/prepa_medi.htm)
• Ultra-high dilution effects
• Final product
• World Market
• USA
Evidence??
• In vitro studies
• Animal studies
• Human studies
• Meta-analyses of human studies
• Implausibility, entrenched skeptics and
overenthusiastic zealots
In: Vallance AK. J Alt Compl Med 1998;4:49-76.
In: Vallance AK. J Alt Compl Med 1998;4:49-76.
In: Vallance AK. J Alt Compl Med 1998;4:49-76.
Reilly et al. Lancet
1994;344:1601-06
asthma
Linde et al. Lancet. 1997 Sep 20;350(9081):834-43
.
: Barnes et al. J Clin Gastroenterol. 1999;25(4):628-
33. Homeopathy and postoperative ileus
Jacobs et al. Pediatr Infect Dis J. 2003;22:229-34.
Jacobs et al. J Alt Compl Med 2000;6:131-139 n=126 in Nepal
Jacobs et al. Pediatr Infec Dis 2001;20:177-183. N=75
Jacobs et al. Pediatr Infec Dis 2001;20:177-183. N=75
Shang et al.
Lancet
2005;366:726-
732
Odds ratio for large, high quality trials (the lower the value the higher the
benefit):
Homeopath. N=8 OR=0.88
Conventional. N=6 OR=0.58
Conclusions: “clinical effects of homeopathy are placebo effects”
Critique: how about giving the OR for all included studies and also the
OR for the”higher quality” studies (n=21 for homeopathy and n=9 for
conventional). The selection of “clinical topics” for study seem to favor
conventional drugs, e.g. respiratory infections.
Shang et al. Lancet 2005;366:726-732
http://www.homeopathicpharmacy.org/index.
htm
Haworth
Press 2007
Probiotics Terms:
•Probiotic – Probiotics are live microorganisms (bacteria
or yeasts) which, when administered in adequate amounts,
confer a health benefit on the host
•Prebiotic - nutritional supplement taken to increase the
amounts of beneficial bacterial in the gut or vagina.
Example “FOS” (fructose oligosaccharides)
•Biotherapeutic agent - microorganism used for specific
therapeutic activity in humans
•Nutriceutical - food products with beneficial effects in
preventing or treating diseases
Predominant Flora: Stomach
Stomach (0-103 cfu/ml):
Gram+ aerobes,
Lactobacillus &
Streptococcus
Predominant Flora: Vagina
Vagina: diverse aerobes & anaerobes including
Lactobacillus jensenii, Lactobacillus acidophilus,
Lactobacillus casei.
Predominant Flora: Urinary Tract
Kidneys: sterile
Bladder: sterile
Urethra: 101-102 E. coli
Predominant Flora: Intestines
Small intestine:
Proximal ileum (103-104 cfu/ml)
aerobic Gram+
Distal ileum (1011-1012 cfu/ml)
Gram- anaerobes
Colon (1011-1012 cfu/ml):
Bacteroides, Eubacteria,
Peptostreptococci, E. coli,
Bifidobacterium, Fusobacteria
Functions of Normal Flora
• Digestion
• Production of vitamins
• Mucosal maturation
• Stimulate Immune System
• Attachment
• Intestinal transit
• Colonization resistance
Use of Probiotics for infections in Controlled Trials
in Humans
•Prevention of Diarrhea
•Antibiotic associated diarrhea
•infantile diarrhea
•traveler’s diarrhea
•Treatment of Diarrhea
• acute diarrhea
•Clostridium difficile disease
•HIV associated diarrhea
•Inflammatory Bowel Diseases
•Bacterial Vaginosis
Stop
Antibiotic
Start
Antibiotic
Start
yeast or
placebo
Stop
Study
yeast or placebo continued for 14d
Saccharomyces boulardii and Antibiotic Associated
Diarrhea in Hospitalized Patients
N=180; site: University of Washington
Surawicz et al., Gastroenterol. 1989;96:981
Surawicz et al., Gastroenterol. 1989;96:981
Stop
Antibiotic
Start
Antibiotic
Start yeast
or placebo
Stop
Study
yeast or placebo
continued for 3d
Saccharomyces boulardii and Beta lactam Antibiotic
Associated Diarrhea in Hospitalized Patients
N=193; site: University of Washington, University of
Kentucky
McFarland et al. Am J Gastroenterol 1995;90:439-448
McFarland et
al. Am J
Gastroenterol
1995;90:439-
448
Antibiotic Associated Diarrhea McFarland LV. Am J Gastroenterol 2006;101:812-822
Lactobacillus GG & Prevention of
Infantile Nosocomial Diarrhea [Methods]
• DBPC in Poland
• 81 hospitalized children (1-36 months
old)
• No diarrhea on admission
• Randomized during stay:
– L. GG (12 x 109 CFU/d)
– Placebo
Szajewska H. J Pediatr 2001;138:361-5.
Lactobacillus GG & Prevention of
Infantile Nosocomial Diarrhea [Results]
6.7*
2.2*
33.3
16.7
*p<0.05
L. GG (n=45) Placebo
(n=36)
Szajewska H. J Pediatr 2001;138:361-5.
Probiotic Prevention of Traveler’s Diarrhea
NYC travelers to developing countries; n=225 (Hilton et al. J.
Travel Med 1997;4:41-43)
7.4%/exposure day for placebo
3.9%/exposure day for Lactobacillus GG
(p=0.05)
Austrian travelers to Turkey; n-1016 (Kollaritsch et al. Fortschr
Med 1993;111:152-156)
39.1% placebo
28.7% S. boulardii (p=0.02)
Lactobacilli and Pediatric Diarrhea Treatment
(L. rhamnosus and L. reuteri in hospital setting)
N=69 Rosenfeldt et al., Pediatr Infec Dis 2002;21:411
Huang, et al., Digestive Diseases and Sciences, Vol.47, No. 11 (Nov 2002)
McFarland et
al., JAMA; 271,
1913-1918,
(1994).
S. boulardii & High Dose
Vancomycin for Recurrent C. difficile
Disease
50%
16.7%
*
Surawicz CM. Clin Infect Dis 2000;31:1012-7.
S. boulardii
(n=18)
Placebo
(n=14)
*p=0.05
Other Uses for Probiotics –•Crohn’s Disease-see slide
•Ulcerative Colitis-see slide
•Irritable Bowel Syndrome-see slide
•Allergy/Exema-see slide
•Pouchitis-VSL#3 mixture is effective in reducing inflammation
•Lactose Intolerance-yogurt helps somewhat
•Bacterial Vaginosis-speeds recovery and decreases recurrence
•Respiratory infections in children*-one study showed 17%
decrease risk in those taking Lactobacillus GG probiotic milk product
•Dental caries*
•High Cholesterol*
•Urinary Tract Infections*
•Helicobacter pylori*
•Candida vaginal infections*
*Limited evidence
From Elmer et al.
The Power of
Probiotics
Haworth Press
2007
O’Mahony et al.
Gastroenterology
2005;128:541-551
IBS n=77, 8 weeks
Table 6.1. Controlled clinical trials evaluating probiotics and Crohn’s
disease (from Elmer et al. The Power of Probiotics, Haworth Press 2007)
Probiotic N Result Ref
L. rhamnosus GG 45 10.5% placebo
16.6% LGG, ns Prantera 7
L. rhamnosus GG 11 2/4 relapse placebo
3/5 relapse LGG, ns Schultz 8
Saccharomyces boulardii 17 4.6 stools/day placebo
3.3 stools/day in Sb* Plein 9
Saccharomyces boulardii 32 6/16 relapse in mesalamine
1/16 relapse in mesalamine/Sb Guslandi 10
E. coli Nissle 1917 28 7/12 relapse in prednisone
4/12 relapse in prednisone/Ec Malchow 11
* probiotic significantly better than control, p<0.05; ns=probiotic not significantly different
than control
Table 6.2. Clinical trials evaluating probiotics and ulcerative colitis (from Elmer et al. The Power
of Probiotics Haworth Press 2007)
Probiotic N Result Ref
E. coli (Nissle 1917) 116 73% relapse in mesalamine
67% relapse in Ec, ns Rembacken 16
E. coli (Nissle 1917) 103 11% relapse in mesalamine
16% relapse in Ec, ns Kruis 17
E. coli (Nissle 1917) 327 36% relapse in mesalamine
45% relapse in Ec, ns Kruis 18
Saccharomyces boulardii 24 17/24 had successful outcome Guslandi 10
VSL#3 (mix) 20 15/20 had no relapse in 12 months Venturi 19
ns= probiotic not significantly different than standard treatment
Lactobacillus GG to Prevent
Infantile Atopic Disease
• DBPC in Finland
• Family history atopic disease
(eczema, allergic rhinitis, asthma)
• Mothers randomized:
– Lactobacillus GG (1 x 1010 CFU/d)
– Placebo
• Mothers treated 2-4 weeks before delivery
Infants treated for 6 months
• Followed for 2 years
Kalliomaki M. Lancet 2001;357:1076-9
Lactobacillus GG and
Infantile Atopic Disease [Results]
23%
*
46%
Kalliomaki M. Lancet 2001;357:1076-9
*p=0.008
L. GG
(n=64)
Placebo
(n=68)
Multiple Mechanisms of
Action
Resistance is Infrequent
Use May Reduce
Exposure to Antibiotics
Delivery of Microbial
Enzymes
Well Tolerated
Benefit to Risk Ration is
Favorable
Few Controlled Trials
Persistence Possible
Translocation Possible
Transfer of Resistance
Plasmids?
Infection Possible
Quality Control Issues
Regulatory Issues in USA
Advantages Disadvantages
Potential Advantages and
Disadvantages of Probiotics
Evidence supporting commercially available (USA) probiotics*
NA
Fair
Fair
None
None
NA
NA
NA
NA
Fair
NA
Fair
IBS
Crohns
UC
GoodLimitedNANAC. dif
FairFairNANATraveler
diarrhea
GoodGoodNANAAcute
pediatric
GoodGoodNANAAcute
Adult
GoodGoodGoodUnevenAAD
condition VSL#3 L. reueri LGG Sb
NA=not available (no studies), None=negative studies
Probiotics Summary
•Living microorganisms with multiple mechanisms
of action
•Good safety profile
•Some applications to prevent and treat infectious
diseases
•An alternative to antibiotics in some situations
•May have other applications, e.g. allergy, cancer,
colitis, Crohn’s Disease, Ulcerative Colitis, IBS
•Product selection is very important
Recommended