University of Western OntarioDeparment of Physiology and Pharmacology

Toxicology of Natural Sourced Medicine

Jacob MatusinecIsboset Nuñez Luna

Monica Rosas CalderónKristine Smit

(March 31th,2011)

Homeopathy

Homeopathy

• Founded by Samuel Hahnemann in the late 18th century

• Hahnemann had some prior training in conventional medicine but he found the practice barbaric and cruel .

• Greatest popularity in 19th century with a revival in the late 20th century.

“Homeopathy watching the Horrors of Allopathy”

Benefits of Homeopathy

• Generally less invasive and has less side effects than conventional medicine.

• Associated with healthier lifestyles

• Patients often do report improved symptoms

• Even if unsupported by Medical Community it’s not “hurting anyone” (some debate)

Potential criticisms of Homeopathy

• Lacks scientific evidence

• Experiments supporting homeopathy often poorly conducted and noreplicable by the scientific community

• The “Three Pillars” of homeopathy are in conflict with the ideology that makes up Modern Science

THREE PILLARS OF HOMEOPATHY

1. The principal of “Similars”

• Remedy causes symptoms similar to the disease in healthy people.

• Quinine and Malaria—cured malaria but caused feverish symptoms in healthy individuals

THREE PILLARS OF HOMEOPATHY

2. The Vital Force

• Harmonize a person on all levels of their being

• Diseases result from disharmonized Vital Force

• Based on a belief system rather than science

• Belief system that has a long history dating back to the Hippocrates.

THREE PILLARS OF HOMEOPATHY

3. “Potentization”

1CONCENTRATION

POTE

NCY

THREE PILLARS OF HOMEOPATHY3. “Potentization”

• Greater potency is achieved as the solution becomes diluted and violently agitated.

• Most debated aspect of homeopathy.

• Many studies done with differential results

• Results tend to depend on the experimenter.

Potentiation Concentration Scale• D scale: denotes the extent of dilution, i.e. D10

concentration=10-10

• C scale: denotes the number of 1:100 dilutions performed.

• D60=C30: Dilution advocated by Hahnemann for most purposes

• C15: very unlikely that any of the original molecules of mother tincture still remaining.

Explanations for Potentiation• Human basophil degranulation triggered by

very dilute antiserum against IgE. Davern E, et al.

• Many other studies found similar results even at dilutions that could probabilistically do not contain any parent molecules.

• Usually explained by the concept of “water memory”

History of the Memory of Water• Jacques Benveniste (March 1935–October

2004) • Benveniste J. Platelet-activating factor, a new mediator of

anaphylaxis and immune complex deposition from rabbit and human basophiles. Nature 1974; 249: 581-582.

“Homeopathy is still not understood, however his efforts started a new era of rigorous scientific investigation of the field”

- Alex Tournier (founding director of the Homeopathy Research Institute)

History of the Memory of Water

• Davenas E, Beauvais F, Amara J et al. Human basophil degranulation triggered by very dilute antiserum against IgE. Nature 1988; 334: 287-290.

• “Specific information must have been transmitted during the dilution /shaking process via some molecular organization occurring in the water”

History of the Memory of Water

• “There were no methodological flaws apparent at the time.” –James Maddox, Nature Editor

• "There are good and particular reasons why prudent people should, for the time being, suspend judgment“ –JM

• Committee: – James Randi: magician-cum-paranormal researcher– Walter Stewart: physicist and freelance debunker

at the US NIH

History of the Memory of Water

• No memory effect was observed in the blinded experiments.

• Although no fraud was found, the lack of reproducibility led Nature to conclude that there was no substantial basis for Benveniste’s claim.

History of the Memory of Water

• Benveniste and several collaborators worked to find the underlying mechanisms to the results on his original paper.

• Jacques started working with homeopath E. Attias

• “Digital Biology: biological interactions could be digitized”

History of the Memory of Water• J. Benveniste; P. Jurgens, W. Hsueh and J. Aissa (February 21–

26, 1997). "Transatlantic Transfer of Digitized Antigen Signal by Telephone Link". Journal of Allergy and Clinical Immunology.

• J. Benveniste; Aissa, J., Guillonnet. "The molecular signal is not functional in the absence of "informed water"". Medical Hypotheses 54

• J. Benveniste; Thomas Y, Schiff M, Belkadi L, Jurgens P, Kahhak L (2000). "Activation of human neutrophils by electronically transmitted phorbol-myristate acetate". FASEB Journal 13 (1): 33–39

Homeopathy Research

Homeopathy Research1. Experimental research – study

efficacy of homeopathic remedies

2. Basic research – elucidate nature of homeopathic remedies

3. Clinical trials – studies clinical efficacy

4. Theoretical models

EXPERIMENTAL RESEARCHin vitro, cell systems, or in vivo

• Many models (both plant and animal) exist but only a few have been replicated independently (and quality often poor)

• Examples: – Jacques Benveniste (1988) – IgE degranulation– Independent replication of more recent studies

• Crosslinking of IgE molecules triggers granule exocytosis with the release of histamine and loss of metachromatic straining of basophil granules by a basic dyeSerially diluted anti-IgE antiserum & measured basophil degranulation at each concentration

•

•

Results• Successive peaks of degranulation from 40-

60% of the basophils over dilutions of anti-IgE that range from 102 to 10120

• Less than one molecule of Ab is present when anti-IgE antiserum is diluted to 1014

“Strengths”• Control: cells incubated

in conditions identical to those with anti-IgE antiserum gave no significant degranulation (antihuman IgG antiserum)

• Blind double-coded procedures

• 6 different laboratories (in 4 countries)

HOWEVER…• Observer bias• Some participating

laboratories withdrew because effect not consistent with results (not reported)

• Variability of the positive results was smaller than the statistically expected error or microscopical cell count and found no effect of higher dilutions

More Recently (2005)…

• Staining and microscopical counting of basophils prone to subjective influences (even if method blinded)

• Experimenters used flow-cytometry to measure basophil degranulation– Determines % CD63-expressing basophils (those activated)– CD63 expression directly correlates with histamine release

• All experiments performed with a blinded and randomised arrangement of dilutions and controls

• Aimed to independently replicate former studies, which showed similar findings as Benveniste

Results• In contrast to former studies, no large effect of

highly diluted histamine solutions on anti-IgE induced basophil degranulation was found

BASIC RESEARCHelucidating the nature of homeopathic remedies…

• To understand mechanism, need to find a plausible theory and experimental backing to clarify how a highly diluted substance can affect a biological system– Must explain how a biological effect can be

brought about without a sufficient number of molecules of the active agent (found in homeopathetic remedies)

• Many scientists Homeopathy violates natural laws and thus any effect must be a placebo effect

• Public & some physicians use of and belief in effectiveness of homeopathy is widespread

• Is the effect seen with homeopathic remedies equivalent to that seen with placebo?

CLINICAL RESEARCH

If the hypothesis that all clinical effects of homeopathy are due to placebo is true:

1. All properly conducted place-controlled trials on homeopathy would be comparing one placebo to another

2. Thus, overall results should vary randomly around a zero difference between groups

• Results not compatible with placebo hypothesis

• However, insufficient evidence that any single type of homeopathic treatment is clearly effective in any one clinical condition

Systemic Reviews of Clinical Trials on Homeopathy for Specific Conditions

Author Indication N and trial type

Conclusions

Taylor et. al.

Allergic conditions

4 RCTs Isopathic nosodes different from placebo on both subjective and objective measures

✔

Jacobs et. al.

Childhood diarrhea

3 RCTs Individualized homeopathic treatment decreases the duration and number of stools in children with acute diarrhea, but sample size small

✔

Ernst Delayed-conset muscle soreness

8 double-blinded trials

Evidence does not support hypothesis that homeopathic remedies are affective for muscle soreness

✗

Vickers & Smith

Influenza-like syndrome

7 RCTs Probably reduces duration of influenza-like syndromes; further trials needed

✔

Barnes et. al.

Postoperative ileus

4 RCTs; 2 CCTs

Available evidence positive but several caveats preclude definitive conclusion

✔

• Efficacy/effectiveness paradox: Disputed evidence that homeopathy is different from placebo yet there is documented usefulness in general practice• ~70% of all patients using homeopathy report they are

considerably improved after treatment (effects remain stable during follow-up periods of 2-5 years)

• Before clinical homeopathy research can proceed with success, needs a viable theory…

THEORETICAL MODELS

• Local–Conventional scientific positivism

• Non-local: quantum theoretical concepts–Complementarity– Entanglement

Local Mechanisms

• Homeopathic remedies behave in a way similar to any other medicine

• The production process produces some kind of template, image, or imprint of the original substance, and this “information” is the active ingredient

Local Mechanisms

• Hydrogen bonds and van der Waal’s interactions

• Electric fields can be modified and modulated by their surrounding

• Laws of thermodynamics?

Examples of local mechanisms

• Remaining material on surfaces• Nanobubbles• Remaining particle clusters• Ethanol solution complexity• Natural water clusters redox molecules

produced from water

Non-local Hypotheses

• “Correlations are somehow established between patient, practitioner and remedy, ultimately leading to an observed change in the patient’s state of health”.

• Even more controversial than local mechanisms: quantum theory applicable in our macroscopic domain??

Non-local Hypotheses

• “Quantum entanglement: property of the quantum mechanical state of a system containing two or more objects, where the objects that make up the system are linked in such a way that the quantum state of any of them cannot be adequately described without full mention of the others, even if the individual objects are spatially separated.”

Water Memory

Empirical Approaches

• Dr. Masaru Emoto.

• He claims about the «resonance» present in words and how these vibrations change in health and disease.

Emoto’s experimentsRice experiment

Three separate treatments to beakers containing rice and water:

1. Thank the flask or say something nice

2. Tell nasty and rude phrases.

3. Ignore it.

Emotto’s Water Crystals (2003)

• 2000 people (Tokyo) prayed to water samples stored on a electromagnetic shielded room. (CA,USA).

• Control samples were in other place.• Pictures of both samples were blindly taken.• After that, the pictures were shown to 100 judges.

(They did not know which crystal was fro which sample)

• Statistically, judges prefer the prayed crystal.

• Shape dependant on the kind of vibration given to the water sample.

Emoto’s experimentsWater crystals

Water memory explanation?

• In 2003, the physics journal: Physica published an experiment on water memory

• Louis Rey.• Thermoluminescence:• The technique involves bathing a chilled sample

with radiation. When the sample is warmed up, the stored energy is released as light in a pattern that reflects the atomic structure of the sample

• “Much to our surprise, the thermoluminescence glows of the three systems were substantially different”

• Control – Double distilled water

• Deuterium – Different arrengement of the bonds.

• 10x 10-5 M of Sodium Chloride and Lithium Chloride.

Water memory explanation?

Water memory explanation?

What did they measure?

Zinc aggregates – Non Noble metals

Gold aggregates – Noble metals

SAED (Selected Area Electron Diffraction)

What info we could get from this paper…? #1

• The change in the properties of the treated water (sucussion) is dependant on time.

• Sucussion or shaking leads to the formation of clusters.

How are these clusters formed?Theodore Grotthus (1806)

• The shaking of

homeopathic dilutions generate dissipative structures.

• “The physicochemical parameters electrical conductivity and heat of mixing are in fact functions of the number, size and shape of the dissipative structures”

Expert Opinions Against Homeopathy

• Steven Novella, Yale University, New Haven, CT.

• The law of similars & law of Infintesimals: no biological plausability.

• Homeopathy is still a philosophy-based medicine

• Hahnemann had his theory of illness, largely based on the notion of miasms.

• Theorists invoking quantum mechanics?

• Donald Marcus. Baylor University, Waco, TX.

• Professor Ernst, Exeter University in England: based on over 20 reviews since 1997 believes there is no evidence homeopathic remedies differ from placebos

• ENHS conclusion: insufficient evidence to support the use of homeopathy.

• The Lancet: “there’s no point in making further investments in research in clinical trials in homeopathy.”

Expert Opinions Against Homeopathy

• No FDA regulations• Safety concern: some homeopathic practioners

recommend against vaccination.• Some people who practice homeopathy are

unqualified to perform general medical evaluations and may miss serious and treatable conditions.

• The Heisenberg principle concerns atomic and subatomic particles and it does not invalidate Newtonian physics: no justification for taking this concept from physics and applying it to health care.

Expert Opinions Against Homeopathy

Is Homeopathy Unethical?• Unethical aspects of homeopathic dentistry

• Homeopathic doctors/hospitals relatively common and there are a fair amount of homeopathic dentists in the UK.

• Many documented effects of homeopathy attributed to placebo and the fact that Homeopathic professionals do not acknowledge this is against ethical guidelines defined by the Society of Homeopaths

• Most studies referenced for the benefits of homeopathic medicine have since been discredited by scientific community.

• “At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. “

From the prospective of Scientific Community

Conclusion

• Jury is still out on whether or not “water memory” truly exists.

• More research needed, but as of today Potentiation and the other pillars of homeopathy are not supported by the scientific community.

Conclusion

• Some empirical evidence shows structural cahnge in water but biological plausibility still uncertain.

• Both Homeopathic practitioners and scientific community remain steadfast in their beliefs.

• Possible that the truth lies somewhere between these two extremes

References• Davenas E, Beauvais F, Amara J, Oberbaum M, Robinzon B, Miadonna

A, Tedeschi A, Pomeranz B, Fortner P and Belon P (1988) Human basophil degranulation triggered by very dilute antiserum against IgE. Nature 333:816-818.

• Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M and Kessler RC (1998) Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 280:1569-1575.

• Elia V, Baiano S, Duro I, Napoli E, Niccoli M and Nonatelli L (2004) Permanent physico-chemical properties of extremely diluted aqueous solutions of homeopathic medicines. Homeopathy 93:144-150.

• Elia V, Baiano S, Duro I, Napoli E, Niccoli M and Nonatelli L (2004) Permanent physico-chemical properties of extremely diluted aqueous solutions of homeopathic medicines. Homeopathy 93:144-150.

References• Elia V, Napoli E and Germano R (2007) The 'Memory of Water': an almost

deciphered enigma. Dissipative structures in extremely dilute aqueous solutions. Homeopathy 96:163-169.

• Guggisberg AG, Baumgartner SM, Tschopp CM and Heusser P (2005) Replication study concerning the effects of homeopathic dilutions of histamine on human basophil degranulation in vitro. Complement Ther Med 13:91-100.

• Kleijnen J, Knipschild P and ter Riet G (1991) Clinical trials of homoeopathy. BMJ 302:316-323.

• Maddox J, Randi J and Stewart WW (1988) "High-dilution" experiments a delusion. Nature 334:287-291.

• Milgrom LR (2009) The eternal closure of the biased mind? The clinical and scientific relevance of biophysics, infinitesimal dilutions, and the memory of water. J Altern Complement Med 15:1255-1257.

References• Milgrom LR (2006) Is homeopathy possible? J R Soc Promot Health

126:211-218.

• Milgrom LR (2006) Towards a new model of the homeopathic process based on quantum field theory. Forsch Komplementmed 13:174-183.

• Radin D, Hayssen G, Emoto M and Kizu T (2006) Double-blind test of the effects of distant intention on water crystal formation. Explore (NY) 2:408-411.

• Shaw D (2010) Unethical aspects of homeopathic dentistry. Br Dent J 209:493-496.

• Walach H, Jonas WB, Ives J, van Wijk R and Weingartner O (2005) Research on homeopathy: state of the art. J Altern Complement Med 11:813-829.