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