Homeopathic Products. Evidence??

Transcription

1 Homeopathic Products Principle of analogy or Law of Similars Small or infinitesimal doses (3X-30C) Avogadro s number=6x10 23 = ~23X Succussion and potentization (see eo/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

2 In: Vallance AK. J Alt Compl Med 1998;4: In: Vallance AK. J Alt Compl Med 1998;4:49-76.

3 In: Vallance AK. J Alt Compl Med 1998;4: Reilly et al. Lancet 1994;344: asthma

4 Linde et al. Lancet Sep 20;350(9081): : Barnes et al. J Clin Gastroenterol. 1999;25(4): Homeopathy and postoperative ileus

5 Jacobs et al. Pediatr Infect Dis J. 2003;22: Jacobs et al. J Alt Compl Med 2000;6: n=126 in Nepal

6 Jacobs et al. Pediatr Infec Dis 2001;20: N=75 Jacobs et al. Pediatr Infec Dis 2001;20: N=75

7 Shang et al. Lancet 2005;366: Shang et al. Lancet 2005;366: Odds ratio for large, high quality trials (the lower the value the higher the benefit): Homeopath. N=8 Conventional. N=6 OR=0.88 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.

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9 htm Haworth Press 2007

10 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 ( cfu/ml): Gram+ aerobes, Lactobacillus & Streptococcus

11 Predominant Flora: Vagina Vagina: diverse aerobes & anaerobes including Lactobacillus jensenii, Lactobacillus acidophilus, Lactobacillus casei. Predominant Flora: Urinary Tract Kidneys: sterile Bladder: sterile Urethra: E. coli

12 Predominant Flora: Intestines Small intestine: Proximal ileum ( cfu/ml) aerobic Gram+ Distal ileum ( cfu/ml) Gram- anaerobes Colon ( 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

13 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 Saccharomyces boulardii and Antibiotic Associated Diarrhea in Hospitalized Patients N=180; site: University of Washington Start Antibiotic Stop Antibiotic Stop Study yeast or placebo continued for 14d Start yeast or placebo Surawicz et al., Gastroenterol. 1989;96:981

14 Surawicz et al., Gastroenterol. 1989;96:981 Start Antibiotic Saccharomyces boulardii and Beta lactam Antibiotic Associated Diarrhea in Hospitalized Patients N=193; site: University of Washington, University of Kentucky Stop Antibiotic Stop Study Start yeast or placebo yeast or placebo continued for 3d McFarland et al. Am J Gastroenterol 1995;90:

15 McFarland et al. Am J Gastroenterol 1995;90: Antibiotic Associated Diarrhea McFarland LV. Am J Gastroenterol 2006;101:

16 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 10 9 CFU/d) Placebo Szajewska H. J Pediatr 2001;138: Lactobacillus GG & Prevention of Infantile Nosocomial Diarrhea [Results] 33.3 *p< * 2.2* L. GG (n=45) Placebo (n=36) Szajewska H. J Pediatr 2001;138:361-5.

17 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: ) 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

18 Huang, et al., Digestive Diseases and Sciences, Vol.47, No. 11 (Nov 2002)

19 McFarland et al., JAMA; 271, , (1994). S. boulardii & High Dose Vancomycin for Recurrent C. difficile Disease 50% *p= % * Placebo (n=14) S. boulardii (n=18) Surawicz CM. Clin Infect Dis 2000;31:

20 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

21 From Elmer et al. The Power of Probiotics Haworth Press 2007 O Mahony et al. Gastroenterology 2005;128: IBS n=77, 8 weeks

22 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 % placebo 16.6% LGG, ns Prantera 7 L. rhamnosus GG 11 2/4 relapse placebo Saccharomyces boulardii stools/day placebo 3/5 relapse LGG, ns Schultz 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 /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) % relapse in mesalamine 67% relapse in Ec, ns Rembacken 16 E. coli (Nissle 1917) % relapse in mesalamine 16% relapse in Ec, ns Kruis 17 E. coli (Nissle 1917) % 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

23 Lactobacillus GG to Prevent Infantile Atopic Disease DBPC in Finland Family history atopic disease (eczema, allergic rhinitis, asthma) Mothers randomized: Lactobacillus GG (1 x CFU/d) Placebo Mothers treated 2-4 weeks before delivery Infants treated for 6 months Followed for 2 years Kalliomaki M. Lancet 2001;357: Lactobacillus GG and Infantile Atopic Disease [Results] *p= % 23% * L. GG (n=64) Placebo (n=68) Kalliomaki M. Lancet 2001;357:1076-9

24 Advantages Multiple Mechanisms of Action Resistance is Infrequent Use May Reduce Exposure to Antibiotics Delivery of Microbial Enzymes Well Tolerated Potential Advantages and Disadvantages of Probiotics Benefit to Risk Ration is Favorable Disadvantages Few Controlled Trials Persistence Possible Translocation Possible Transfer of Resistance Plasmids? Infection Possible Quality Control Issues Regulatory Issues in USA

25 Evidence supporting commercially available (USA) probiotics* condition VSL#3 L. reueri LGG Sb AAD Uneven Good Good Good Acute Adult Good Good Acute pediatric Good Good Traveler diarrhea Fair Fair C. dif Limited Good IBS Fair None Crohns UC Fair None Fair Fair =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