Source: https://thehomeopathiccollege.org/homeo-research/prover-susceptibility-homeopathic-research/
Timestamp: 2019-04-19 04:43:34+00:00

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Over the past decade, scientists and medical researchers have used sophisticated research methodologies in order to prove or disprove the efficacy of homeopathy. Based on their findings, editors of prestigious medical journals have concluded that there is no scientific validity to our therapeutic approach . Given the high stakes of this research, the investigators’ command of the homeopathic subject matter and the underlying assumptions reflected in these studies need to be carefully examined.
Homeopathy is based on the discovery that a drug will cure if it can evoke symptoms similar to those of the disease. Therefore, to select the proper curative remedy, drug symptoms must be known. In 1776, Samuel C. Hahnemann, M.D. began to test medical drugs to determine the symptoms they could elicit. Over several decades of painstaking research, he perfected the homeopathic “law of proving”—the verifiable fact that all medicinal substances can cause symptoms specific to the substance. Hahnemann conducted most of his proving tests with diluted medicines (that is, the crude substances diluted in either water, alcohol or both). In the later years of his life, he advocated the use of substances potentized (diluted and succussed) beyond Avogadro’s number, namely in the 30C potency.
Modern pathogenetic research presumes that the “proving hypothesis” is the notion that a drug can evoke symptoms in a high dilution (such as a 30C). This is erroneous. To test the “law of proving,” i.e. to prove the claim that medicinal substances evoke symptoms in healthy persons, the trials should be conducted with crude substances (whether diluted or not). Testing remedies in high potencies does not examine this central tenet of homeopathy—it tests the effect of high potencies!
Moreover, in applying modern quantitative methodology to the testing of potentized remedies, these researchers have sacrificed several vital aspects of the original proving protocol that negatively affected the outcome of their investigations. They fail to take into consideration (a) the susceptibility of the provers and (b) the need to increase the dose systematically until symptoms develop. The prover susceptibility and the ascending dose are essential aspects of the homeopathic proving protocol, and without incorporating these, the conclusions of these trials are worthless.
For purposes of this review, I examined nine studies published in various academic journals between 1993 and the present time [3-11]. Of the trials examined, only two found substantial effects from high potencies in randomly selected, healthy test subjects when compared with placebo. Seven out of nine studies found little or no effect [3-9].
Walach, et al.  claims to investigate the proving hypothesis—the “pillar of homeopathy.” They concluded that “homeopathic proving symptoms appear to be specific to the medicine,” however, “rival hypotheses cannot be ruled out” because of small samples. The study also investigated whether any effects were due to “local” rather than “non-local” factors, following up on a hypothesis by Milgrom that ultramolecular effects could be explained in the context of the homeopath-patient relationship .
All of the nine trials share the premise that high potencies should bring out proving symptoms in healthy subjects. This premise is based on the fact that most modern provings make use of high potencies. However, the Hahnemannian law of proving does not stipulate the use of potentized substances. It simply states that every medicinal substance brings about specific signs and symptoms when tested on a healthy person (healthy being defined as “free from signs and symptoms of disease”).
For the first three decades of his research, Hahnemann recorded the symptoms of medicinal substances from toxicological reports and from simple tests of the crude substances on himself and his volunteers . Most Hahnemannian provings were made with more or less diluted crude substances. Eventually he noticed that high potencies brought out more symptoms in sensitive subjects than the crude dose and than even the lower potencies. The higher potencies yielded more subtle symptoms such as peculiar subjective sensations and mental changes that were valuable clinically for selecting the characteristic remedy for a disorder.
In order to bring out the full range of symptoms during provings, by the fifth edition of the Organon, Hahnemann recommended using the 30C potency, in a daily dose of 4-6 granules for several days (§128)[14, 15]. He chose the 30C potency precisely because he had found that, by experiment, at this level it evokes no primary or secondary symptoms or other side effects in most people. So it is far from surprising that the authors of the majority of studies cited did not find any statistically significant evidence of effect from high potencies when testing them on a random population.
In fact, the principles of “similars” and of “proving” exist independently of the “principle of potentization.” The proving hypothesis is not dependent on the use of potentized substances. Crude substances may be used either homeopathically on the sick to treat disease, or on healthy persons to prove a remedy. The above trials are not tests of the proving hypothesis as claimed, but tests of the ultramolecular or ultra-high-potency hypothesis. The scientists’ reasoning is this: Since homeopaths claim the proving principles also apply to high potencies, if the high potencies don’t yield positive results, the validity of the homeopathic principles is called into question. This is erroneous reasoning. Why use substances whose properties are unknown or controversial to test something you could test using ordinary and known crude substances? Why test the homeopathic “law of proving” using “ultramolecular” substances rather than crude substances?
Ultramolecular (potentized) substances have been the main preoccupation of scientists investigating homeopathy because they do not see any “rational basis” for their use. In a review of studies , Walach, et al. blame homeopaths for their own preoccupation: “It is precisely homeopaths’ emphasis on so-called high potencies (i.e., remedies succussed and diluted beyond Avogadro’s number) that creates tension with modern science because no accepted rational theory exists that could explain increased therapeutic effect with decreasing amounts of the active agent, even to the point of there being no molecules of the initial agent present at all.” Actually it is the researchers scrutinizing homeopathic concepts who overemphasize the ultramolecular substance.
So, when Walach, et al.  claim that “homeopathy lies on two principles: the law of similars and the potentization of homeopathic remedies,” they were making a misleading statement. Homeopathy is the law of similars. Additionally, there is the law of potentization.
Interestingly, many scientist investigating homeopathy seem to prefer the terms “ultramolecular” and “ultra-diluted” to “potentized.” In doing so they introduce a bias, implying implausibility. During the process of potentization, homeopathic pharmacists dilute the crude substance in a solvent, such as water, step by step, and agitate the mixture between each step. They may continue beyond the point when the last molecule of the substance has been diluted out (Avogadro’s number). Scientists refer to this point and beyond as “ultramolecular dilutions.” Terms like these emphasize the ultra-high degree of dilution, ignoring the function of agitation or “succussion.” According to Hahnemann, the effect of the high-potency medicine lies in its high state of agitation, not in its level of dilution. The terms “potentization” or “dynamization” used by Hahnemann imply that their efficacy lies in the development of a force field that evokes a physiological effect even after the substance has been diluted out completely. Modern science has yet to confirm this hypothesis, though there is plenty of evidence in its favor, for example [see references 17, 18, 19, 20, 21].
For nearly 200 years, homeopathic medical scientists have painstakingly duplicated Hahnemann’s drug testing protocols and repeatedly confirmed his observations. It was homeopaths that conducted the first double-blinded experimental study in the history of pharmacology, a proving trial conducted in Nürnberg, Germany in 1835 . The above studies are an attempt to scrutinize 200 years of sound scientific research. Are they reinventing the wheel? A closer look at Hahnemann’s proving protocol shows modern trials to be sadly lacking.
While it is desirable to use a high-potency for provings, the Hahnemannian proving guidelines require that the proper dose necessary to induce symptoms be used. Susceptibility of provers to a substance depends on (a) the relative toxicity of the substance, (b) the size of the dose, and (c) the sensitivity of the provers. To put this into contemporary language, Hahnemann was fully aware of the dose-response relationship of toxic and potentized substances, and of the differing susceptibility of individuals.
In §121 of the sixth and final edition of the Organon of Medicine [23, 24], Hahnemann laid the theoretical foundations for successful proving experiments: “In proving medicines to test their effect on the healthy organism, one must bear in mind that strong, so-called heroic substances bring about alterations in health even in small doses, even on robust people; milder ones must be given in larger doses in these experiments; the weakest ones, on the other hand, reveal their true action only when tested on delicate, susceptible, and sensitive people who are free from disease” (3; § 121).
Hahnemann explained that some symptoms could only be elicited in persons with “idiosyncrasies.” He points out that there are people who are basically healthy but “faint from the smell of roses and others who can become sick in many other ways, from eating mussels, crab, barbell, roe, from touching the leaves of some varieties of sumac, etc.” (§117; a, b). Such sensitive people were to be used to bring out the symptoms of the weakest/most dilute of medicinal substances.
For example, in a case from my own practice , a patient had multiple food allergies, reacted violently to vegetable substances, and vomited every vegetable he ate. After taking repeated doses of Bryonia alba 30C (prepared from wild hops, a vegetable substance) for a cold, he developed severe symptoms of arthritis. He had red, swollen, stiff and aching joints, fever with intense thirst, scanty urine, and was just barely able to move. After learning of his peculiar susceptibility and recent doses of Bryonia, I offered him one whiff of spirits of Camphor, which antidotes the effects of all vegetable remedies , and by the end of the consultation his symptoms had disappeared and he was walking normally. Obviously, this individual had the necessary idiosyncrasy to become a prover for Bryonia 30C, and probably for many other vegetable substances in high-potency.
• “Even a very moderate dose is often sufficient if the subject is sensitive enough…” (§130).
• “In this way the effect of an unknown medicine, even the mildest, will be revealed, especially if tested on sensitive subjects…” (§132).
• “If one takes pains to facilitate the investigation by choosing a truthful, sensitive subject…” (§137).
• “…the best will always be those that the healthy, unprejudiced, conscientious, sensitive physician undertakes on himself…” (§141).
The substance Bryonia alba used in one of the trials  is not a heroic poison, but a relatively mild one [13, 26]. Toxicological reports show no serious life-threatening effects from the crude form. To prove the remedy Bryonia 30C on an average population, a high dose, such as a few drops of the mother tincture or the very low x-potency could be used. But if you diluted it further, by the time you reached the 6x potency, most people would experience no symptoms. This potency is widely available over the counter. It would be unreasonable to expect, as two of the trials have done, that the 12C potency of such a mild substance (a dilution slightly above Avogadro’s number) would bring out symptoms in the average population. However, it will do so in “delicate, susceptible, and sensitive people” (3, §121).
Hahnemann also recommended that the dose be adjusted to make up for the difference in sensitivity. He suggested, “since one cannot know this in advance, it is highly advisable to start with a small dose of medicine for everybody and, where appropriate and necessary, increase it from day to day.” He advised, “if only weak effects appear from such a dose, one can increase it daily by a few granules until the effects become clearer and stronger, and the changes in health are more perceptible.” He concluded, “in that way the effect of an unknown medicine, even the mildest, will be revealed, especially if tested on sensitive subjects” (§ 132).
There is no indication that the investigators in any of the cited trials applied these proving guidelines, i.e. that they pre-tested provers for their (a) general sensitivity or for (b) any specific susceptibility to the (1) substance, (2) potency, or (3) dose in question, or advised their subjects to individualize and (c) gradually increase the dose until symptoms appeared.
In order to scrutinize the homeopathic proving hypothesis properly, a well-designed trial would have taken into consideration the entirety of the homeopathic proving guidelines and incorporated the full set of instructions to the minutest detail. It would have conducted the trials with sufficient doses of the remedies, selected only intelligent, conscientious, healthy, and above all, sensitive individuals, and tried several different medicines in the 30C potency to allow for general sensitivity and substance-specific differences in provers’ susceptibility, and would have required that doses be increased until symptoms develop.
The researchers of all trials under review with negative results chose to ignore in their trial design the dose-susceptibility relationship. They randomly selected “provers” without regard to their sensitivity, and gave all of them the same dose. Clearly, they did not even examine the Hahnemannian proving protocols. They did not pay attention to the recommendations designed to evoke symptoms from high potencies. While the methodologies used could possibly find some efficacy if one were to engage in a mere “symptom gathering exercise,” in a trial expressly aimed at scrutinizing the conceptual foundation of homeopathy, the approach amounts to a significant error of omission.
Some of the authors of the cited studies mentioned the factors of prover sensitivity and dose. However, they failed to incorporate these factors in their study design. Vickers, et al.  commented on the rationale of testing the proving hypothesis by using a crude substance as “plausible,” yet they wrongly inferred from their own negative results that this challenges the “proving hypothesis.” They, too, failed to differentiate the proving principle from the ultra-high-potency principle.
When a research team incorporated even a portion of one of these factors , they obtained positive results. This is the only one of the nine trials that applied a flexible dosage method by repeating the remedies until symptoms appeared. But this is not the ascending dose method Hahnemann had recommended. While this trial showed positive results, one could not expect this method to consistently evoke symptoms in randomly selected subjects. Most “robust” subjects without “idiosyncrasies” would never get symptoms, because they would need a dose that is specific to their relatively lower susceptibility.
This clearly indicates that some researchers were aware of the need to individualize the dose. Yet they falsely claim that Hahnemann’s dosage protocol requires a repetition of the same dose, rather than an increasing dose, until symptoms appear. The scientists’ claim that they used a fixed duration of a dose “to avoid overdosing” is very interesting considering the flexible method is designed to avoid overdosing, and the danger of overdosing is much greater in using the same dose for a fixed duration because the more sensitive subject may not need a dose for the full duration. According to protocol, you give a sufficient dose to bring out symptoms, then you stop. This avoids overdosing.
Hahnemann took the issue of dose very seriously. In addition to his dosage recommendations for proving experiments, he also left detailed instructions on the individualization of the dose when treating sensitive patients. He pointed out that some patients needed considerably smaller doses, and recommended using the olfactory dose, or, if necessary, additional dilutions of a given potency, should proving symptoms appear in these sensitive patients (§ 248).
Some researchers drew conclusions about the relative number of persons that “prove” a remedy. Goodyear, et al.  state that “only a small percentage of individuals actively prove; Walach estimates that 1% of individuals proved in his study while we have suggested that between 10 and 20% are likely to prove.” This flawed expectation is apparently based on the results of previous trials and their common failure to incorporate selection criteria for prover susceptibility and the “ascending dose” method. At least in theory, all healthy persons prove highly active substances in high-potency, provided they are sensitive, and provided they take the remedy in a dose adequate for their individual susceptibility.
We can deduce from standard homeopathic theory that an average dose of a high-potency can be expected to bring out symptoms in an average number of provers in a select, susceptible population. That same dose will predictably yield smaller than average results when tried on the general (random) population. This means, in a randomized, placebo-controlled study, the difference between placebo and verum would likely be weak to insignificant. This is exactly what the researchers found, thus proving the homeopathic theory to be correct!
It is noteworthy that several of the above trials were conducted with significant cooperation from homeopaths and homeopathic students who should be familiar with individualization of dose according to sensitivity of the proving subjects. Many otherwise knowledgeable homeopaths who conduct proving experiments apparently still do not make the distinction between potency and dose. One reason for this may be a historical event: the tragic delay in the publication of the sixth edition of the Organon.
When the sixth edition was finally published in German in 1920, nearly 80 years after Dr. Hahnemann’s death, many homeopaths still did not realize that he had made a clear distinction between potency and dose. Mathias Dorsci, Georg von Keller and Gerhard Koehler were some of the first modern day homeopaths to point out the distinction [28, 30, 31]. By 1921 when the English translation first appeared, many homeopaths had already become accustomed to reducing the dose by increasing the potency, basing this practice on James Tyler Kent’s interpretation. Kent maintained that higher and higher potencies should be used to reduce the dose of the remedy to the “minimum dose” .
Hahnemann had made a distinction between a low dose and a high-potency in the fifth edition [14, 15]. He explained it even more clearly in the sixth edition [23, 24]: In §275 he states that when a medicine is homeopathic to the disease, it is harmful in too high a dose. In §276 he adds, “the higher its potency the more harm it does,” and “if the dose is appropriately small, a well-dynamized medicine becomes increasingly curative” (§277). Thus, Hahnemann taught to reduce the risk of harm by diminishing the amount given (by diluting the dose) not by increasing its dynamization or potency, as Kent incorrectly claimed. In the subsequent paragraphs, Hahnemann explains that the appropriate dose depended on the individual sensitivity of a patient and can only be determined by pure experimentation on each individual patient.
To prevent further harm during treatment, Hahnemann developed a new potentization method: He increased the steps of dilution from 100 to 50,000, thus reducing the risk of harm from the lower potencies (§270). However, when the sixth edition finally appeared, homeopaths mistook the new technique of these Q-potencies (quinquagintamillesimal, also improperly called LM-potencies) for the mere “plussing” (a small increase in potency) of a C-potency remedy [30, 32] and ignored it.
The distinction between potency and dose and its individualization during treatment or proving has not yet found its way into all homeopathic educational institutions. Some homeopaths appear to be either unaware of the distinction or ignore it in their practices. Even a recently published web-based set of guidelines titled ECCH Recommended Guidelines for Good Provings by the European Council for Classical Homeopathy contains no reference to Hahnemann’s individualization requirements in selecting provers. There is also no mention of the Hahnemannian controls – the ascending dose to accommodate for the individual susceptibility of provers (Organon, §132).
The revelations on the researchers’ failure to incorporate Hahnemannian controls in their pathogenetic trials by no means exonerate current provings or much of the modern homeopathic database from the accusation of questionable validity. On the contrary—the latter themselves deviate from the Hahnemannian standards. I therefore join Vickers, et al.  in the question of what this means for the reliability and completeness of modern-day homeopathic provings.
Unfortunately, errors of omission have led to false trial results that have dire cumulative consequences. ESM de Lange de-Klerk, in his commentary on one of the trials in the journal Focus on Alternative and Complementary Therapies, summarized the results of the study with the statement, “there is no evidence that potentized Bryonia was different from placebo” . The headline in the same issue for a review of the second trial read, “symptoms produced from homeopathic Belladonna 30CH are likely due to chance” . The reviewers deemed both studies “carefully conducted.” Given that most of the trials found no efficacy for “ultramolecular” pathogenetic effects, supposedly “the pillar of homeopathy,” it is no surprise that scientists around the world have concluded that homeopathy is simply a placebo effect.
In the nine trials examined, researchers failed to find evidence for the homeopathic proving hypothesis because they started with the wrong premise: They confused the proving hypothesis with the efficacy of high potencies. They botched their attempts to scrutinize high-potency provings because they failed to incorporate conditions and controls that are an inherent part of homeopathic provings. Such errors have consequences.
With only two out of nine trials finding evidence of a “proving effect,” the casual observer is left with the impression that ultra-high potencies are suspect, and that the proving hypothesis, and thus all of homeopathy, is a myth. It is not surprising that many scientists have concluded that there is no rational basis for homeopathy. Researchers have accomplished this impression by deviating from the original Hahnemannian proving protocols and further aided it by a confusion of concepts and terminology that serves to obscure these errors of fact and omission.
Though the negative results of the studies under review actually proved the correctness of the homeopathic proving theory, unfortunately their authors seem unaware of this fact. There is no indication anyone outside the homeopathic community has taken notice. The significance of the errors in these trials extends beyond the problem of proving accuracy and the impact it unquestionably has on future studies. Improperly designed studies yielding false negatives due to inadequate or incomplete understanding or application of homeopathic theory have a devastating effect on the scientific community’s perception of homeopathy that will be difficult to reverse. And, unless the errors are exposed, they will reverberate into future policy guidelines drawn by governments and regulatory bodies.
In summary, while the trials’ formal quantitative methodology was of above-average quality, they fell short on substance. We have entered an era when the sophistication of the methodology used in investigating alternative systems of medicine is sometimes greater than the investigator’s grasp of the subject matter they set out to examine. It is unfortunate that nine inadequate trial designs may have contributed to a rejection of the homeopathic healing system for all the wrong reasons.
1. Editorial. The End of Homeopathy. Lancet 2005; 366:690.
2. Dantas F, Fisher P. A systematic review of homoeopathic pathogenetic trials (“provings”) published in the United Kingdom from 1945 to 1995. In Ernst E, Hahn EG, eds. Homeopathy a critical appraisal. London: Butterworth-Heineman, 1998:69-97.
3. Walach H, Hieber S, Ernst-Hieber E. Effects of Belladonna 12 CH and 30CH in healthy volunteers: a multiple, single-case experiment in randomization design. N: Bastied M, ed. Signs and Images: Selected Papers from the 7th and 8th GIRI Meeting [Montpelier, France, Nov 20-21, 1993, and Jerusalem, Israel, Dec 10-11, 1994]. Dordrecht, Boston and London: Kluwer, 1997:215-226.
4. Walach H. Does a highly diluted homeopathic drug act as a placebo in healthy volunteers? Experimental study of Belladonna 30C in double-blind crossover design- a pilot study. J Psychosom Res 1993; 37(8):851-860.
6. Walach H, Köster H, Hennig T, Haag G. The effects of homeopathic belladonna 30CH in healthy volunteers- a randomized, double-blind experiment. J Psychosom Res 2001; 50:155-150.
7. Vickers A, McCarne R, Fisher P, van Haselen R. Can homeopaths detect homeopathic medicines? A pilot study for a randomised, double-blind, placebo-controlled investigation of the proving hypothesis. Br Homeopathy J. 2001 Jul; 90(3):115-6.
8. Vickers AJ, van Haselen R, Heger M. Can homeopathically prepared mercury cause symptoms in Healthy volunteers? A randomized, double-blind placebo-controlled trial. J Alt Comp Med 2001;7(2):141-148.
10. Walach H, Sherr J, Schneider R, Shabi R, Bond A, Rieberer G. Homeopathic Proving Symptoms: result of a local, non-local, or placebo process? A blinded, placebo-controlled pilot study. Homeopathy 2004; 93:179-185.
11. Möllinger H, Schneider R, Löffel M, Walach H. A double-blind, randomized, homeopathic pathogenetic trial with health persons: comparing two high potencies. Forsch Komplementarmed Klass Naturheilkd. 2004 Oct; 11(5):274-80.
13. Hahnemann S. Materia Medica Pura. Transl. by R.E. Dudgeon, with annot. by Richard Hughes. Vols. I and II. B. Jain Publishers, New Delhi, India 1989.
14. Hahnemann S Organon der Heilkunst, 5. Auflage. Dresden und Leipzig, 1833.
15. Hahnemann S The Organon of The Healing Art, 5th ed. Transl. by B M Fincke. Transcr. fr. the original manuscript. Publ. by J Winston, Great Auk Publishing, Wellington, New Zealand 2004.
16. Walach H, Jonas WB, Ives J, van Wijk R, Weingärtner O. Research on Homeopathy: State of the Art. J Alt Comp Med 2005;11(5):813-829.
17. Sukul NC, Ghosh S, Sukul A, Sinhabaru SP, Variation in Fourier Infrared Spectra in some homeopathic potencies and their diluent media. J Alt Comp Med 2005;11(5):807-812.
18. Rey L, Thermoluminescense of ultra-high dilutions of lithium chloride and sodium chloride. Physica A 2003; 323:67-74.
19. Demangeat JL, Demangeat D, Poitivin B, et al. Low-field NMR water proton longitudinal relaxation in ultrahigh diluted aqueous solutions of silica-lactose prepared in glass material for pharmaceutical use. Appl. Magnetc Resonance 2004; 26:465-481.
20. Belon P, Cumps J, Ennis M, et al. Histamine dilutions modulate basophil activations. Inflamm Res 2004; 53:181-188.
21. Benveniste J. From Water to Digital Biology. Network 1999; 69:11-14.
22. Stolberg, M Homeopathy on Trial: the first double-blind experiment of medical history in the year 1835 (in German) Münchner Medizinische Wochenschrift 1996; 138:364-366.
23. Hahnemann S., Organon of Medicine, Sixth Edition, transl. Künzli/Naudé, Cooper Publishing, Blaine Washington, 1982.
24. Hahnemann S. Organon der Heilkunst. Textkritische Ausgabe der 6. Auflage. Bearbeitet und herausgegeben von J M Schmidt, Karl F. Haug Verlag, Heidelberg. 1992.
25. Mueller M. Case study: Proving symptoms in a patient with severe vegetable food allergies after Bryonia 30C. Unpublished.
26. Boericke W, Pocket Manual of Homeopathic Materia Medica, with repertory by O Boericke., Boericke and Tafel, Santo Rosa, California 1927:127.
27. Vithoulkas G, The questions of provings in homeopathy. Focus Altern Complement Ther 1998; 3:27-28.
28. Dorsci M Handbuch der Homöopathie. ISBN 3-8094-1100-0.
29. Kent JT Lectures on homeopathic philosophy. North Atlantic Books, Berkeley, California 1979: 220-23.
30. von Keller G. Über Q-Potenzen, Vorlesung, Fortbildungsveranstaltung des Landesverbandes Baden-Württemberg, 1988.
32. Dishington L, Lecture. Brit Hom J 15:227.
33. Focus on Alternative and Complementary Therapies, December 2001 6(4): 265-67.

References: §121
 § 121
 §121
 §275
 §276
 §132