Complementary Therapies in Medicine (2007) 15, 128—138

The in vitro evidence for an effect of high homeopathic potencies—–A systematic review of the literature
Claudia M. Witt a,∗, Michael Bluth b, Henning Albrecht c, Thorolf E.R. Weißhuhn a, Stephan Baumgartner d, Stefan N. Willich a
Institute for Social Medicine, Epidemiology and Health Economics, Charit´ University Medical Center, e D-10098 Berlin, Germany b Klinik f¨r Tumorbiologie, D-Freiburg/Br, Germany u c Karl and Veronica Carstens-Foundation, D-Essen, Germany d Institute for Complementary Medicine (KIKOM), University of Bern, CH-Bern, Germany
Available online 28 March 2007 KEYWORDS
Homeopathy; Potency; Dynamization; Basic research; Quality assessment; Quality score; Modified SAPEH; BEPEV; Cell-free systems; Non-cellular; Cultured cells; Basophiles; Neutrophiles; Lymphocytes; In vitro
a

Summary Objective: Systematic assessment of the in vitro research on high potency effects. Method: Publications of experiments were collected through databases, experts, previous reviews, citation tracking. Inclusion criteria: stepwise agitated dilutions <10−23 ; cells or molecules from human or animal. Experiments were assessed with the modified SAPEH score. Results: From 75 publications, 67 experiments (1/3 of them replications) were evaluated. Nearly 3/4 of them found a high potency effect, and 2/3 of those 18 that scored 6 points or more and controlled contamination. Nearly 3/4 of all replications were positive. Design and experimental models of the reviewed experiments were inhomogenous, most were performed on basophiles. Conclusions: Even experiments with a high methodological standard could demonstrate an effect of high potencies. No positive result was stable enough to be reproduced by all investigators. A general adoption of succussed controls, randomization and blinding would strengthen the evidence of future experiments. © 2007 Elsevier Ltd. All rights reserved.

Introduction
Homeopathic remedies are prepared (‘potentized’ or ‘dynamized’) in steps of alternately diluting and succussing a homeopathic stock1 (historically known as ‘mother tincture’). After several steps,

∗ Corresponding author. Tel.: +49 30 450529011; fax: +49 30 450529902. E-mail address: claudia.witt@charite.de (C.M. Witt).

0965-2299/$ — see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.ctim.2007.01.011

In vitro research on high potencies the remedies reach calculatory dilutions beyond Avogadro’s number, implying a non-molecular action of remedies with specific healing properties. Research in this field arranges around three core problems2 : (1) What are the therapeutic effects of homeopathic remedies? (2) What are the specific characteristics of potencies? (3) Through what mechanism(s) do they influence the organism? Relating to (1) and (3), in vitro research searches for effects of potentized remedies on molecular or cellular systems. Reducing complexity this way allows a higher degree of standardization than clinical research, and may eventually provide model systems to reveal the mode of action of high dilutions devoid of pharmacologically active molecules. Previous reviews of the field have been either descriptions of individual experiments without systematic evaluation3—7 , investigations of only the independence of replications8 , or do not present details and rationales of their scoring procedure.9 Other restrictions had been set on publications language3,4,6 or research area,7,8 so that a both broad and systematic assessment with transparent criteria does not exist. In this evaluation we therefore systematically assessed the in vitro research on effects of high potencies of a stock preparation by using a score system. Additionally, we tried to identify experimental models that provide reproducible results or promising approaches that should be replicated.

129 2005 by searching for ‘hom¨opathie + basic o research + experimental + in vitro’ in each of the following fields: immunology, toxicology, pharmacology, neurology, biochemistry. Medline® was searched for publications of the years 1966 until December 2005 using MeSH and full text terms in various spellings. Searched was for ‘homeopathy’ combined with each of the following terms: ‘in vitro’; ‘cell culture’; ‘tissue culture’; ‘cells, cultured’; ‘granulocyte’; ‘lymphocyte’; ‘macrophage’; ‘neutrophil’; ‘basophil’; ‘enzyme’; ‘biomolecule’; ‘immunocompetent’. Amed® (Allied and Alternative Medicine) was searched from 1985 to December 2005 using the same search as in Medline. Previous reviews,3—6,8,9 and all obtained publications were screened for further references. In addition, we asked experts for information.

Data extraction
From the identified references, those too short for a sensible scoring were excluded, among them were all abstracts. From publications that were mostly or fully identical or obviously referring to identical experiments only the most detailed description was included. One author (MB) extracted data and scored the experiments except his own paper12 that was scored by another author (SB) who did not participate in this work, the data were discussed with a second author (CMW). For each experiment the following data were extracted: publication, objective, technique, findings, substance tested, control or comparison, and solvent of potentizing, together with additional information of interest. All identified publications were classified by system: non-cellular systems (enzymes), or cellular systems of the categories cultured cells, erythrocytes, basophile granulocytes, neutrophile granulocytes, and lymphocytes/mononuclear cells (including experiments with both neutrophiles and lymphocytes). Strategies involved either cellular or cell-free systems, the former from healthy or from pathological donators. Indirect effects in which the potency modified the action of a stimulus on the target system were set apart from direct effects where the homeopathic preparation acted on the target system directly. Replications were recognized when they investigated the same experimental setup (cell, enzyme, stimulant, noxa, . . .) with the same homeopathic remedy in high (but not necessarily identical) potency. They were operationally defined as ‘independent’ if the publication had a different first author and less than half of their authors had published experiments with this model before.8 Finally,

Methods
Inclusion criteria and data sources
We searched for written publications of in vitro investigations on high potencies. In vitro was defined as ‘concerning cellular or subcellular entities in isolation from a living organism’. This included cells (also from cultures) or molecules, but not isolated organs. All systems had to be of human or animal origin. Pathological materials such as cancer cells or cells from allergic donators were accepted. Pretreatment before cell extraction, such as intoxication or sensitization, was allowed, but the application of homeopathic preparations had to be in vitro only. Tested remedies had to include high potencies that imply a calculatory dilution of at least 10−23 (e.g. ≥D23, ≥C12). Remedy mixtures (‘complex remedies’) were allowed. No other restrictions were imposed; all publication languages were included. References from the Basic Research Database of the Karl and Veronica Carstens-Foundation, D-Essen,10,11 were collected until December

130
Table 1 Item ObjectivesP Controls Declared Adequate Inadequate BlindingM RandomizationM ConsistencyM Experiment standardizationS Medium Incubation StatisticsM ResultsP
P Presentation, incubation. M

C.M. Witt et al.
The modified SAPEH (score for assessment of physical experiments on homeopathy) Points 1 1 +1 −1 1 1 1 1 1 1 1
M Methodology, S Standardization:

Criteria Explicit statement what problem or hypothesis was investigated Stated use of controls Succussed or correspondingly potentized solvent Not checking contamination, e.g. unsuccussed Blinding of experimenter/tester State of the art samples randomization Similar results in two or more experiments or test series Use of a buffer or buffered medium if necessary Standardized temperature and incubation time Statistical analysis declared or described Comprehensible presentation of results
quality constructs built into the score. Modifications check for buffer and

it was noted whether the publications stated or implied that the findings supported the existence of effects of high potencies for at least one of the tested potencies, or, in multicenter trials, at least one laboratory.

Modified SAPEH assessment
To provide a transparent and differentiated insight into the strengths and weaknesses of the assessed research, we applied a modified version of the Score for Assessment of Physical Experiments on Homeopathy (SAPEH, Table 1). SAPEH had been developed to assess the quality of physical research in homeopathy.13 It is based on three quality constructs — methodology, experiment standardization, presentation — that divide into 8 items, checking for 10 criteria. Each item scores 1 point for an affirmative answer, except controls and experiment standardization with 2 points each. The methodology items check that the experimental design uses techniques to control factors that may cause bias (e.g. systematic or random errors). Mentioning controls scores 1 point that is subtracted again if their nature allows for chemical differences to the potencies. Identical composition is assumed if controls have undergone a similar contaminant-affecting preparation (succussion or potentizing)13 as the test potencies. It would earn 2 controls points, accepted are all meaningful descriptions such as ‘‘produced like the verum’’ or ‘‘succussed (shaken, vortexed, sonicated, . . .) medium’’. Further methodology items cover blinding (preventing handling differences and bias effects), randomization (to prevent systematical errors), consistency (internal replications,

ensuring test system stability), and the use of statistics. Experiment standardization was adapted to the in vitro field, instead of the somewhat unspecific original criteria ‘external factors’ and ‘experimental setup’ that can affect results, the item now checks for the use of a buffer or buffered medium, and for standardized temperature and incubation time. The remaining communication about the experiment is covered by presentation of objectives and results, which have to be reasonably detailed and understandable. The modified SAPEH should be read at item level to assess an experiment. The total SAPEH score and its subscores support only rough global impressions and should always be accompanied by score details. For the purposes of the present study, 6 or 7 points with controls of equal contamination would indicate a reasonable control for bias, and >7 points (including 2 for controls) would strengthen this.

Results
Literature
We identified and obtained 75 publications12,14—87 that fulfilled inclusion criteria, among them one sufficiently detailed correspondence.45 Seventeen redundant publications were identified (Fig. 1): Three doctoral theses12,33,35 were included that cover and extend the content of eight omitted papers: 71—75, 76; 77, and 78, respectively. Two summaries79,87 of otherwise included experiments were ignored. From another summary62 those parts

In vitro research on high potencies

131 with seemingly identical content, the first listed in each of the following groups was included: 31/80; 41/81; 66/83; 67/82; 68/84/85; 36/86. Two papers48,50 overlapped in content, the more detailed later one was included, whereas from the earlier publication we included only one additional experiment. Of two articles about the same research, two experiments were reviewed from the earlier publication14 and one additional experiment from the other.15 From one paper37 one already published experiment was ignored in favor of the earlier publication.34 Multiple experiments in a single publication12,19,37,42,62,70 were scored individually, resulting in 67 experiments from 58 publications. Table 2 (published in online version at http://www.sciencedirect.com/as supplementary data) lists the details, together with some contextual information to provide a broader overview. The included publications had appeared mostly in journal articles (n = 46), 25 of them were of

Figure 1 Publications and experiments.

were excluded that were less detailed than earlier papers.56,57 Where the analyzed data set of an earlier publication58 seemed to be not identical to the summary data88 we scored both. Of publications
Table 3

Modified SAPEH scores and classifications of reviewed experiments

132
Table 3 (Continued)

C.M. Witt et al.

a

Publications languages: E = English, F = French, G = German. Research strategy: d/cf = direct effect on cell-free system; d/c/h = direct effect on cells from healthy probands; d/c/p = direct effects on cells from pathological donators; i/c/h = indirect effects on cells from healthy probands; i/c/p = indirect effects on cells from pathological donators. c For criteria, quality constructs (P = Presentation, M = Methodology, S = Standardization) and score points see text and Table 1. d 0* = (+1−1), see text. e Findings support the existence of a high potency effect (+) or not (−) (stated or implied). ** Only for histamine part.
b

the mainstream: organs of conventional medicine (n = 12), sciences in general (n = 7), or biological medicine (n = 6). The other 21 articles appeared in periodicals of homeopathy in general (n = 15), homeopathic research (n = 3), or complementary and alternative medicine (n = 3). The remaining 12 publications were dissertations (n = 7, including 1 comparable thesis for a homeopathy diploma (28)), congress presentations (n = 3), and books (n = 2). Most authors had published in English (57%), followed by German (25%) and French (18%).

Experiments
The investigated systems were mostly basophile granulocytes (42%), non-cellular systems (27%), and cultured cells (19%). Seldom lymphocytes (6%), erythrocytes (3%), or neutrophiles (3%) were chosen.

Measuring indirect effects on healthy proband cells was the most favoured approach (37%), followed by direct effects on cell-free systems (27%), indirect effects on cells from pathological sources (19%), direct effects on cells from healthy (10%) and pathological (8%) donators. Table 3 lists the classifications of the assessed experiments. Presentation was sufficiently good for most (79%) experiments (Table 3); 16% lacked a clear description of either objectives or results and 4% of both. Randomization was only reported for 18% and blinding for 33% of the experiments. For most investigations at least one successful replication was stated (83%), 31% checked contamination with succussed controls, in 4% no use of controls was stated. Statistical evaluation was common (76%). In 73% of the experiments buffer and incubation were standardized, in 22% only one of these was mentioned,

In vitro research on high potencies and in 4% none. The overall modified SAPEH mean was 6.1 (S.D. ± 1.9, median 6.0). Most experiments were done with basophiles models, here also the most positive results were found. From the 67 assessed experiments, 73% stated an effect of high potencies. So did 68% of the 18 experiments with succussed controls and a modified SAPEH score of at least 6 points. Eight of these 19 experiments have not been replicated. Of all scored experiments, 33% were replications. Positive results were reported for 73% of the replications, and for 18% of those with 6 or more points and succussed controls. Replications were most often performed with flow cytometry on basophiles, here mostly by independent teams and with positive results except one.63 All attempts to replicate effects on hydrolase activity were independent and successful but one.12 The action of anti-IgE potencies on basophiles was only reproduced by the same team.

133 But the existence of more negative studies would not rebut those high-scoring works that demonstrated an effect of potentizing beyond Avogadro’s number. Compared to a previous evaluation of physical research on high potencies13 we found in the present review more in vitro investigations for the same time frame (until 2001, 53 experiments in vitro versus 37 in physics). We observed also a greater percentage of experiments scoring at least 6 points with succussed controls (26% versus 14%), more replications (25% versus 8%), and more publications in renowned periodicals. Applying a score to assess publications systematically is not common in basic research on homeopathy. Although scores have limitations we decided for it because of the benefits of systematizing the synopsis and making the assessment criteria transparent. Most relevant works are well known which made blinded scoring or split assessments of methods and results impossible. We tried to achieve high internal consistency by having all scoring done by one investigator. This review is limited to the presentation of experiments in the literature, as common for reviews, presuming correctness and accuracy of the reports, but it can never be sufficiently detailed to set up reproductions. Because SAPEH was designed for quick and easy use, we accepted a limitation that lies in not accounting for the number of repetitions, which would have to be observed on several levels. The number of independently produced potencies, test runs per potency, samples per test run, variations in date or location, etc. would require a much more detailed score system. From the mostly self-explaining SAPEH score the items blinding, standardization, and controls require some discussion. In order to identify results that were the most robust to bias and systematic errors91 we included blinding as a criterion. Although probably rare, unconscious bias may creep in through processes that involve human interpretation or judgment, or minute differences in handling. The additional standardization through a buffered medium reduces the variability of results that otherwise might mask a difference between sample types. To prove that high potencies have a specific effect they should only differ from controls in being a potentized stock preparation. Several types of controls or comparisons are available: stock preparation (original material of remedy preparation), unsuccussed solvent, succussed solvent, and another remedy (potency of different stock preparation). A stock preparation would entail gross chemical differences. Untreated solvent has recently been found to be different from a potency

Discussion
We systematically assessed in vitro experiments on high potencies with the modified SAPEH score. The designs of the 67 evaluated experiments were very inhomogenous. We observed an uneven distribution of the investigated systems, ranging from two unrelated experiments each with neutrophile granulocytes or erythrocytes to 28 with basophiles (15 of them being replications). One third of the experiments were replications of earlier research. Nearly 3/4 of the identified experiments found a high potency effect. Even if only those experiments that tried best to exclude bias were considered (SAPEH score of 6 points or more and succussed controls), a positive effect was still demonstrated in more than 2/3 of the experiments. Although it seems unlikely, we could not be totally sure that the results of these experiments are unbiased. Publications on homeopathic research are widely scattered, often not entered into databases, and thus difficult to find. The database of the Karl and Veronica Carstens-Foundation was very helpful. In addition citation tracking and expert contacts enlarged the number of found publications. Presentations at conferences of either basic or clinical research are not too often followed up by journal articles (e.g. only half of the conventional randomized clinical trials89 )—–the reason why we did not restrict our search to full articles. Publication bias that is very likely in the field of homeopathy90 would cause a tendency to positive results. For example, unsuccessful pilot studies in search for a viable test system may not have been published.

134 in the concentration of contaminants that are introduced during the potentizing through interactions of solvent and container material.92 In multi-container potencies (Hahnemann technique), trace element concentrations had reached with the first potency a level that remained constant in higher potencies.39,92 This applied to potentization with standard parameters93 that are commonly adopted in basic research. Differences between untreated and potentized36,37 or simply sonicated94 solvent have been observed in biological activity as well as physical measurements95 , they might be causally linked to contamination.92,95 . Trace elements are the rationale for our emphasis on succussed — better: fully potentized — controls. Other contaminants make the fully identical preparation more desirable, like acetate, formate or lactate from the human skin, or methanol and acetone used for cleaning, all easily being introduced with ordinary handling.96 A second remedy as control might in the lower (material) dilutions have its own interaction with container materials97 , making a solution of which the exact composition is unknown but which is likely to be different from the one of the first potency. Both thus would differ not only in their known initial stock preparation. Moreover, the effect of both potencies on the measurements might be identical which would invalidate a clearly ‘negative’ result to mean merely ‘possibly negative, or possibly positive but differences cancelled out’. For the purposes of the present review we asked for the type of control that allowed the clearest conclusions.

C.M. Witt et al. tion and blinding would strengthen the evidence of further experiments.

Acknowledgments
This work was supported by the Karl und Veronica Carstens-Foundation, D-Essen. We are very grateful to Mrs Hacke from the Karl und Veronica CarstensFoundation who assisted in the literature search. Mrs Menzel from the Charit´ University Medical e Center Library performed the Medline® and Amed® searches.

Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.ctim.2007.01.011.

References
1. European Committee for Homeopathy. Homeopathic thesaurus: keyterms to be used in homeopathy: first multilingual Edition; 2002.URL: www.homeopathyeurope.org. 2. Anagnostatos GS, Pissis P, Viras K. Atomic and nuclear clusters. In: Proceedings of the Second International Conference at Santorini. Santorini, Greece: Springer; 1993. 3. King, G. Experimental investigations for the purpose of scientifical provings of the efficacy of homeopathic preparations. Thesis. Hannover: Tier¨rztliche Hochschule; 1988. a 4. Majerus M. Kritische Begutachtung der wissenschaftlichen Beweisf¨hrung in der hom¨opathischen Grundlagenu o forschung [Critical examination of the scientific evidencing in homeopathic basic research]. Thesis. Tier¨rztliche a Hochschule Hannover; 1990. 5. Righetti M. Forschung in der Hom¨opathie [Research in o homeopathy]. Stuttgart: Burgdorf; 1988. 6. Joguet N. Donn´es r´centes sur la recherche biologique e e et physico-chemique en hom´opathie (1990—1995) [Recent e data about biological and physical-chemical research on homeopathy (1990—1995)]. Thesis. U.F.R. des Sciences Pharmaceutiques; Universit´ Victor Segalen Bordeaux II; e 1996. 7. Bellavite P, Conforti A, Pontarollo F, Ortolani R. Immunology and homeopathy. 2. Cells of the immune system and inflammation. eCam 2006;3(1):13—24. 8. Vickers AJ. Independent replication of pre-clinical research in homeopathy: a systematic review. Forsch Komplement¨rmed 1999;6:311—20. a ´ 9. Tisseyre H. Analyse et evaluation de la recherche fondamentale en hom´opathie: proposition de crit`res e e methodologiques [Analysis and evaluation of basic research in homeopathy: proposal of methodological criteria]. Thesis. Faculte de Pharmacie, Universit´ de Montpellier I; 1996. e 10. Albrecht H, Van Wijk R, Dittloff S. A new database on basic research in homeopathy. Homeopathy 2002;91:162—5. 11. Karl and Veronica Carstens-Foundation. The HomBRexDatabase; 2005. URL: www.carstens-stiftung.de/hombrex.

Conclusions
The reviewed in vitro experiments with high homeopathic potencies were inhomogenous in design and quality. A surprisingly high number of different experimental approaches have been adopted. Two thirds of the experiments with higher scores and contaminant-checking controls demonstrated specific high potency effects. Some of them have also been successfully replicated, but no positive result could be reproduced in all attempts. Among those that have been replicated by independent investigators the action of mercuric bichloride on hydrolases and especially the action of histamine of the Anti-IgE triggered basophile granulocyte degranulation seemed to be the best reproducible. A publication bias in a highly controversial field like homeopathy is not unlikely. More replications should be done independently to establish models that are stable across laboratories and teams. A general adoption of succussed controls, randomiza-

In vitro research on high potencies
12. Bluth M. In-vitro-Forschung mit hom¨opathischen Poteno zen. Ein systematischer Review und eigene Versuche mit zellfreien Systemen [In-vitro-research on homeopathic potencies. A systematic review and own experiments with cell-free systems]. Thesis. Berlin: Institut f¨r u Sozialmedizin, Epidemiologie und Gesundheits¨konomie; o Charit´—Universit¨tsmedizin; 2005. e a 13. Becker-Witt C, Weißhuhn TER, L¨dtke R, Willich SN. Quality u assessment of physical research in homeopathy. J Alt Compl Med 2003;9:113—32. 14. Persson WM, Ginsberg AS. Die Einwirkung von Mikrodosen hom¨opathischer Arzneimittel (chemischer oder pflano zlicher) auf die Fermente Urease und Diastase [The action of microdoses of homeopathic remedies (of chemicals and plants) on the enzymes urease and diastase]. Dt Z Hom 1932;11:97—106. 15. Persson WM. Die Einwirkung von Mikrodosen s¨mtlicher a Arzneimittel und Chemikalien auf Fermente: Urease, Diastase und Trypsin [The effect of microdoses of all remedies and chemicals on ferments: urease, diastase and trypsin]. Arch Int Pharm Th´r 1933;46:249—67. e 16. Persson WM. Die Einwirkung verschiedener Stoffe in kleinen Dosen auf das diastatische Ferment der Muskelgewebe [The effect of several substances in small doses on the diastatic ferment of muscular tissue]. Arch Int Pharm Ther 1938;58:93—102. 17. Boyd WE, Br F. Biochemical and biological evidence of the activity of high potencies. Br Hom J 1954;44:7—44. 18. Kraus JL, Aubin M, Baronnet S, Manlhiot JH, Yaouanc JJ. Action de diff´rentes hauteurs de dilution de Phosphorus e blanc Phosphorus sur la cin´tique d’une r´action enzymae e tique in vitro, impliquant le transfert d’un groupement phosphat´ [Action of different heights of dilutions of white e phosphorus on the enzymatic reaction cinetics in vitro that involve the transfer of a phosphate group]. Ann Hom Franc 1981;23:91—101. 19. Jussal RL, Dua RD, Mishra RK, Meera S, Agarwal A. Effect of ultradilutions on neurotransmitter/enzyme. Hahnemann Gleanings 1984;51:245—50. 20. Petit C, Belon P, Got R. Effect of homoeopathic dilutions on subcellular enzymatic activity. Human Toxicol 1989;8:125—9. 21. Shabir S, Khan S, Begum S, Hashmi RY, Saiphy ZS. Effect of homeopathic drugs on the in vitro activity of alpha amylase from human saliva. Ind J Hom Med 1996;31:93—8. 22. Harisch G, Dittmann J. Untersuchungen zur Wirkung von Ubichinon Injeel und Injeel forte mit zellfreien Systemen [Investigations of the effect of Ubichinon Injeel and Injeel forte with cell-free systems]. Biol Med 1997;26:99—104. 23. Harisch G, Dittmann J. Unterschiedlicher Einfluß von cAMP-Potenzen und cAMP-Verd¨nnungen am Beispiel veru schiedener Enzymsysteme [Different influence of potencies and dilutions of cAMP exemplified on several enzyme systems]. Biol Med 1998;27:55—62. 24. Harisch G, Dittmann J. Aktivit¨tsbestimmungen der Sauren a Phosphatase in Gegenwart von Ubichinon-Einzelpotenzen und Ubichinon-Potenzmischungen [Determination of activity of acid phosphatase in presence of single potencies and potency mixtures of ubiquinone]. Biol Med 1999;28:188—94. 25. Harisch G, Dittmann J. Aktivit¨tsbestimmungen der Sauren a Phosphatase in Gegenwart von cAMP-Einzelpotenzen und cAMP-Potenzmischungen [Determination of activity of acid phosphatase in presence of single potencies and potency mixtures of cAMP]. Biol Med 1999;28:139—46. 26. Dittmann J, Kanapin H, Harisch G. Einfluss ausgew¨hlter a Hom¨opathika auf die katalytische Aktivit¨t der Urikase, o a

135
der sauren Phosphatase und der zytosolischen GlutathionS.Transferasen [Influence of selected homeopathics on the catalytic activity of uricase, acid phosphatase and cytosolic glutathion-S-transferases]. Biol Med 2000;29: 125—31. Sukul NC, Sukul A, Sinhababu SP. Potentized mercuric chloride and mercuric iodide enhance alpha-amylase activity in vitro. Homeopathy 2002;91:217—20. Batello CF. Antioxidante effect in vitro of the homeopathic medicine arsenicum album, cuprum metallicum manganum and zincum metallicum. Thesis. IBEHE — Center of Postgraduation in homeopathy; FACIS — Health Science College of S˜o Paulo; 2003. a van Mansvelt JD, Amons F. Inquiry into the limits of biological effects of chemical compounds in tissue culture. Z Naturforsch 1975;30:643—9. Aubin M, Berjon JJ, Bildet J, Gomez H, Larrue J, Quilichini R. Etude de l’activit´ h´patoprotectrice de Phosphorus sur e e des fragments de foies de rats adultes plac´s en culture e organotypique sur milieu artificiel apr`s intoxication par le e CCL4 [Study of hepatoprotective activity of phosphorus on parts of adult rat livers placed in organotypical culture in artificial environment, after CCl4 intoxication]. Ann Hom Franc 1980;22:25—33. Boiron J, Abecassis J, Cotte J, Bernard AM. L’´tude e de l’action de dilutions hahn´manniennes de chlorure e mercurique sur l’index mitotique de culture de cellules animales [Study of the action of Hahnemannian dilutions of chloride of mercury on the mitotic index of animal cell cultures]. Ann Hom Franc 1981;23:43—9. Kandefer-Szerszen M, Borowska L, Barthel M, Malarcyk E. Einfluss extrem hoher Verd¨nnungen menschlichen u alpha-Interferons auf das Tumorzellwachstum [Influence of extremely high dilutions of human alpha-interferon on tumor cell growth]. Dt J Hom 1993;12:114—28. ` e Delbancut A. Contribution a l’´tude des effets de hautes dilutions de m´taux vis-`-vis de la cytotoxicit´ du cadmium e a e sur cultures de cellules tubulaires r´nales [Contribution to e the study of effects of high dilutions of metals against the cytotoxicity of cadmium on renal tubular cell cultures]. Thesis. U.F.R. des Sciences Pharmaceutiques, Universit´ de e Bordeaux; 1994. Pison U, Steden H, Lais-Schweer L. Der Einfluß stark verd¨nnter hom¨opathischer Arzneimittel auf das u o Zellwachstum von Fibroblasten in vitro [The effect of highly diluted homeopathic remedies on the cell growth of fibroblasts in vitro]. In: Albrecht H, Fr¨hwald M, editors. u Jahrbuch der Karl und Veronica Carstens-Stiftung, Band 1 (1994). Stuttgart: Hippokrates; 1995. p. 69—82. Then C. In-vitro-Untersuchung der Effekte kleinster Entit¨ten von Arsenicum album, Cuprum sulfuricum, Mera curius sublimatus corrosivus und Thuja occidentalis an Zellkulturen mit Hilfe des MTT-Testes [In vitro investigation of effects of smallest entities of Arsenicum album, Cuprum sulfuricum, Mercurius sublimatus corrosivus and Thuja occidentalis on cell cultures by means of the MTT test]. Thesis. M¨nchen-Weihenstephan, Institut f¨r Tierwissenschaften; u u Technische Universit¨t; 1995. a Carmine TC. Effects of high potencies of tumour necrosis factor alpha on H2 O2 production in cultured neuroblastoma cells by enhanced luminol-dependent chemiluminescence (ECL): a possible system for investigating the biological significance of homoeopathic high potencies. Br Hom J 1997;86:67—72. Herberth G, Pison U. Hom¨opathische Arzneimittel in o zellbiologischen Systemen [Homeopathic remedies in cellbiological systems]. In: Albrecht H, Fr¨hwald M, editors. u

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37.

136
Jahrbuch der Karl und Veronica Carstens-Stiftung, Band 5 (1998). Essen: KVC; 1999. p. 77—95. Jonas WB, Lin Y, Tortella F. Neuroprotection from glutamate toxicity with ultra-low dose glutamate. Neuroreport 2001;12:335—9. Marotta D, Marini A, Banaudha K, et al. Non-linear effects of cycloheximide in glutamate-treated cultured rat cerebellar neurons. NeuroToxicology 2002;23:307—12. Murrieta M, Leynadier F, Dry J. D´granulation des e basophiles humains et substances dites hom´opathiques e [Degranulation of human basophiles and substances called homeopathics]. Bull Acad Nat Med 1985;169:619—22. Poitevin B, Aubin M, Benveniste J. Effet d’Apis mellifica sur la d´granulation des basophiles humains in vitro [Effect of e Apis mellifica on the degranulation of human basophiles in vitro]. Hom Franc 1985;73:193—8. Sainte-Laudy J, Belon P. Application de mod`les e ` d‘hypersensibilit´ du type I a l’´tude de l’activit´ e e e de dilutions hahnemanniennes des m´diateurs de cette e hypersensibilit´ [Application of hypersensitivity type I e models on the study of the activity of Hahnemannian dilutions of mediators of this hypersensitivity]. Hom´opathie e 1986;3:40—4. Belon P. Homeopathy and immunology. In: 42nd Congress of the International Homeopathic Medical League 1987. LMHI; 1987. p. 265—70. Davenas E, Beauvais F, Amara J, et al. Human basophil degranulation triggered by very dilute antiserum against IgE. Nature 1988;333:816—8. Metzger H, Dreskin SC. Only the smile is left. Nature 1988;334:375. Poitevin B, Davenas E, Benveniste J. In Vitro immunological degranulation of human basophils is modulated by lung histamine and Apis mellifica. Br J Clin Pharmacol 1988;25:439—44. Ruff F, Dorfman P, Santais MC, Grossriether H, T´tau M. e Effects de dilutions de Pollen, d’Histamine et d’Arsenic: Sur l’histamino-lib´ration in vitro sur sang total de sujets e allergiques [Effects of dilutions of pollen, histamine, and arsenic: on the histamine release in vitro of whole blood from allergic donators]. Cahiers de Biotherapie 1988;98:83—9. Sainte-Laudy J. Inhibition of Basophil Degranulation with Histamine Dilutions. In: Fondation Francaise pour la Recherche en Homeopathie, editor. R´union des 4 et 5 juile let 1989, Communications and Discussions. Lyon: Author’s Edition; 1989. p. 2—25. Benveniste J, Davenas E, Ducot B, Cornillet B, Poitevin B, Spira A. L’agitation de solutions hautement dilu´es e n’induit pas d’activit´ biologique sp´cifique [Agitating e e highly diluted solutions does not induce specific biological activity]. C R l’Acad Paris 1991;312:461—6. Sainte-Laudy J, Sambucy JL, Belon P. Biological activity of ultra low doses. I. Effect of ultra low doses of histamine on human basophil degranulation triggered by D. Pteronyssinus extract. In: Dutremepuich C, editor. Ultra low doses. London, Washington: Taylor & Francis; 1991. p. 127—38. Sainte-Laudy J, Belon P. Biological activity of ultra low doses. II. Effect of ultra low doses of histamine on human basophil degranulation triggered by anti-IgE. In: Doutremepuich C, editor. Ultra low doses. London, Washington: Taylor & Francis; 1991. p. 139—44. Ovelg¨nne JH, Bol A, Hop WCJ, Wijk Rv. Mechanical agitao tion of very dilute antiserum against IgE has no effect on basophil staining properties. Experientia 1992;48:504—8. Hirst SJ, Hayes NA, Burridge J, Pearce FL, Foreman JC. Human basophil degranulation is not triggered

C.M. Witt et al.
by very dilute antiserum against human IgE. Nature 1993;366:525—7. Sainte-Laudy J, Belon P. Inhibition of human basophil activation by high dilutions of histamine. Agents Actions 1993;38:245—7. Sainte-Laudy J, Belon P. Analysis of immunosuppressive activity of serial dilutions of histamine on human basophil activation by flow cytometry. Inflamm Res 1996;45:33—4. Sainte-Laudy J, Belon P. Application of flow cytometry to the analysis of the immunosuppressive effect of histamine dilutions on human basophil activation: effect of cimetidine. Inflamm Res 1997;46:27—8. Belon P, Cumps J, Ennis M, et al. Inhibition of human basophil degranulation by successive histamine dilutions: results of a European multi-centre trial. Inflamm Res 1999;48:17—8. Brown V, Ennis M. Flow-cytometric analysis of basophil activation: inhibition by histamine at conventional and homeopathic concentrations. Inflamm Res 2001;50:47—8. Sainte-Laudy J. Stimulatory effect of high dilutions of histamine on activation of human basophils induced by antiIgE. Inflamm Res 2001;50:63—4. Lorenz I, Schneider EM, Stolz P, Brack A, Strube J. Influence of the diluent on the effect of highly diluted histamine on basophil activation. Homeopathy 2003;92:11—8. Lorenz I, Schneider EM, Stolz P, Brack A, Strube J. Sensitive flow cytometric method to test basophil acitvation influenced by homeopathic histamine dilutions. Forsch Komplement¨rmed Klass Naturheilkd 2003;10:316—24. a Belon P, Cumps J, Ennis M, et al. Histamine dilutions modulate basophil activation. Inflamm Res 2004;53: 181—8. Guggisberg AG, Baumgartner S, Tschopp CM, Heusser P. Replication study concerning the effects of homeopathic dilutions of histamine on human basophil degranulation in vitro. CTIM 2005;13:19—00. Fanselow G. Der Einfluß von Pflanzenextrakten (Echinacea Purpurea, Aristolochia Clematitis) und hom¨opathischer o Medikamente (Acidum Formicicum, Sulfur) auf die Phagozytoseleistung humaner Granulozyten in vitro [Influence of plant extracts (Echinacea Purpurea, Aristolochia Clematitis) and homeopathic remedies (Acidum Formicicum, Sulfur) on phagocytotic activity of human granulocytes in vitro]. Thesis. M¨nchen: Medizinische Fakult¨t; Ludwigu a Maximilians-Universit¨t; 1984. a Chirumbolo S, Signorini A, Bianchi I, Lippi G, Bellavite P. Effects of homeopathic preparations of organic acids and minerals on the oxidative metabolism of human neutrophils. Br Hom J 1993;82:237—44. Bildet J, Dupont H, Aubin M, et al. Action in vitro de dilutions infinitesimales de Phytolacca americana sur la ` transformation lymphoblastique a la phytoh´magglutinine e [In vitro action of infinitesimal dilutions of Phytolacca americana on the transformation of lymphoblasts by phytohemagglutinine]. Hom Franc 1984;72:225—30. Colas H, Aubin M, Picard P, Lebecq JC, Bastide JM. Inhi` bition du test de transformation lymphoblastique (TTL) a la phytoh´magglutinine (PHA) par Phytolacca americana e en dilutions hom´opathiques [Inhibition of lymphoblast e transformation test (LTT) by phythemagglutinine (PHA) through Phytolacca americana in homeopathic dilutions]. Hom Franc 1984;72:219—24. Chirila M, Hristescu S, Manda G, Neagu M, Olinescu A. The action of succussed substance on the human lymfocytes and granulocytis PMN in vitro stimulated with phytohaemagglutinin or zymosan opsonized. In: Proc Congr OMHI. 1990. p. 172—7.

38.

54.

39.

55.

40.

56.

41.

57.

42.

58.

59.

60.

43.

61.

44.

45. 46.

62.

63.

47.

64.

48.

65.

49.

66.

50.

67.

51.

52.

68.

53.

In vitro research on high potencies
69. Gibson SLM, Gibson RG. The effects of homoeopathic potencies of house-dust mite on the migration of housedust-sensitive human leucocytes. Complem Ther Med 1996;4:169—71. 70. Sukul NC, De A, Sinhababu SP, Sukul A. Potentized mercuric chloride and Nux vomica facilitate water permeability in erythrocytes of a fresh-water catfish clarius batrachus under acute ethanol intoxication. J Altern Compl Med 2003;9:719—25. 71. Delbancut A, Dorfman P, Cambar J. Influence de la dur´e du e pr´traitement avec de tr`s basses concentrations de cade e mium sur la cytotoxicit´ induite par le m´tal sur cellules e e tubulaires de rein en culture [Influence of the duration of pretreatment with very low concentrations of cadmium on cytotoxicity induced by the metal and on cultured kidney tubular cells]. In: Delbancut A, Dorfman P, Cambar J, editors. 5th GIRI meeting, 29—30 November, Paris; 1991. p. 37. 72. Delbancut A, Dorfman P, Cambar J. Protective effect of very low concentrations of heavy metals (cadmium and cisplatin) against cytotoxic doses of these metals on renal tubular cell cultures. In: G.I.R.I., editor. 6th GIRI Meeting, 26—27 October 1992. M¨nchen, Germany: GIRI; 1993. u p. 19. 73. Delbancut A, Merlet D, Mellado M, Dorfman P, Cambar J. Etude de l’effect protecteur de tr`s hautes dilutions de cade mium vis-`-vis de concentrations cytotoxiques de ce mˆme a e m´tal sur des cultures cellulaires r´nales [Study of proe e tective effects of very high dilutions of cadmium against the cytotoxic concentration of the same metal on renal tubular cell cultures]. Cahiers de Biotherapie 1993;120: 39—44. 74. Delbancut A, Merlet D, Mellado M, Dorfman P, Cambar J. Nachweis der Schutzwirkung sehr hoher Verd¨nnungen von u Metallen auf mit Cadmium vergiftete Nierenzellkulturen [Proof of protective effect of very high dilutions of metals on cadmium intoxicated renal tubular cell cultures]. Dt J Hom 1995;14:163—75. 75. Delbancut A, Barouillet MP, Cambar J. Evidence and mechanistic approach of the protective effects of heavy metal high dilutions in rodent and in renal cell cultures. In: Signals and images. selected papers from the 7th and 8th GIRI Meeting. Dordrecht: Kluwer; 1997. p. 71—82. 76. Then C, Dittmann J, Sch¨tte A, Bauer J, Harisch G. u In-vitro-Untersuchung zur Wirkung hom¨opathischer Poteno zen von Thuja occidentalis an Zellkulturen mit Hilfe des MTT-Testes [In-vitro investigation on the effect of homeopathic potencies of Thuja occidentalis on cell cultures using the MTT test]. Forsch Komplement¨rmed 1996;3: a 280—7. 77. Then C, Dittmann J, Sch¨tte A, Bauer J, Harisch G. In-vitrou Untersuchung zur Wirkung von Arsenicum-album-Potenzen an Zellkulturen mit Hilfe des MTT-Testes [In-vitro investigation on the effect of potencies of Arsenicum album on cell cultures using the MTT test]. Forsch Komplement¨rmed a 1996;3:222—8. 78. Witt C, Bluth M, L¨dtke R, et al. Does potentized HgCl2 u (‘mercurius corrosivus’) affect the activity of diastase and -amylase? J Alt Compl Med 2006;12:359—65. 79. Dittmann J, Harisch G. Wirkungsunterschiede zwischen Potenzenaccorden und ihren Einzelpotenzen: In-vitroStudien mit cAMP- und Ubichinon-Pr¨paraten [Differences a of efficacity between potency chords and their element potencies: in-vitro studies on preparations of cAMP and ubiqinone]. Biol Med 2000;29:18—23. 80. Cotte J, Bernard A. The effects of mercurius corrosivus hahnemanian potencies upon the multiplication of cultured

137
fibroblasts poisoned with mercury chloride. In: Boiron J, Abecassis J, Belon P, editors. Aspects of research in homeopathy. Lyon: Editions Boiron; 1983. p. 51—9. Poitevin B, Aubin M, Benveniste J. Approche d’une analyse quantitative de l’effet d’Apis mellifica sur la d´granulation e des basophiles humains in vitro. Innov Tech Biol Med 1986;7:64—8. Colas H, Aubin M, Picard P, Lebecq JC, Bastide JM. Inhi` bition du test de transformation lymphoblastique (TTL) a la phytoh´magglutinine (PHA) par Phytolacca americana en e dilutions hom´opathiques [Inhibition of lymphoblast transe formation test (LTT) by phythemagglutinine (PHA) through Phytolacca americana in homeopathic dilutions]. Ann Hom Franc 1975:629—38. Bildet J, Dupont H, Aubin M, et al. Action in vitro de dilutions infinitesimales de Phytolacca americana sur la ` transformation lymphoblastique a la phytoh´magglutinine e [In vitro action of infinitesimal dilutions of Phytolacca americana on the transformation of lymphoblasts by phytohemagglutinine]. Ann Hom Franc 1981;23:102—11. Chirila M, Hristescu S, Manda G, Neagu M, Olinescu A. The action of succussed substances on the human lymphocytes and PMN granulocytes in vitro stimulated with phytohaemagglutinin (PHA) or zymosan opsonized (ZO). In: G.I.R.I., editor. 4th Meeting November 30—December 1, 1990, Maison de la Recherche, Paris. Paris: GIRI; 1990. p. 11. Chirila M, Hristescu S, Manda G, Neagu M, Olinescu A. The in vitro action of a succussed substance on the proliferative response of human lymphocytes stimulated with phytohemagglutinin. Rev Roum M´d Int 1992;30:63—7. e Carmine TC. Bestimmung der H2 O2 -Produktion von Neuroblastomzellen nach Stimulierung mit Hochpotenzen des Zytokins TNF alpha durch Chemolumineszenz: Ein m¨gliches o System zum Wirksamkeitsnachweis hom¨opathischer Hocho potenzen [Chemoluminescence determination of H2 O2 produktion of neuroblastom cells after stimulation with high potencies of the cytokine TNF alpha: a possible system for the proof of efficacy of homeopathic high potencies]. AHZ 1996;241:143—54. Sainte-Laudy J. Modulation of allergen and anti-igE induced human basophil activation by serial histamine dilutions. Inflamm Res 2000;49:S5—6. Baumgartner S, Guggisberg A. Basophilendegranulation, dritter Akt: Hom¨opathie und Basophilenreaktion — o weniger klar, als manche das gerne h¨tten. [Kommena tar zu Belon P, Cumps J, Ennis M, Mannaioni PF, Roberfroid M, Sainte-Laudy J, Wiegant FAC. Histamine dilutions modulate basophil activation. Inflamm Res 2004; 53:181—188] [Basophiles degranulation, third scene: Homeopathy and basophiles reaction — less clear than some would like. (Commentary)]. Forsch Komplement¨rmed a Klass Naturheilkd 2005;12:52—4. Ezzo J, Berman BM, Vickers AJ, Linde K. Complementary medicine and the cochrane collaboration. JAMA 1998;280:1628—30. Shang A, Huwiler-M¨ntener K, Nartey L, et al. Are the u clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet 2005;366:726—32. Baumgartner S, Heusser P, Thurneysen A, Methodological Standards. Problems in preclinical homoeopathic potency research. Forsch Komplement¨rmed 1998;5:27—32. a Witt C, L¨dtke R, Weißhuhn T, Willich S. The role of trace u elements in homeopathic preparations and the influence of container material, storage duration, and potentisation. Forsch Komplement¨rmed 2006;13:15—21. a

81.

82.

83.

84.

85.

86.

87.

88.

89.

90.

91.

92.

138
93. Bundesminister f¨r Gesundheit und Soziales. Hom¨opau o thisches Arzneimittelbuch [Homoeopathic Pharmacopoeia]. Stuttgart: Deutscher Apotheker-Verlag; 1978. 94. Haseba T, Matsushita K, Asakura T, et al. Diminution of biological reactivity of ethanol by changing the solution structure by weak ultrasonication. Alcoholism Clin Exp Res 1993;17:963—7. 95. Witt C, L¨dtke R, Weißhuhn TER, Willich SN. High homeu opathic potencies are different from potentized solvent

C.M. Witt et al.
when investigated with the REDEM technology. Forsch Komplement¨rmed Klass Naturheilkd 2005;12:6—13. a 96. Anick DJ. High sensitivity 1 H-NMR spectroscopy of homeopathic remedies made in water. MBMC Compl Alt Med 2004;4:15. URL: http://www.biomedcentral.com/14726882/4/15. 97. Walach H, Jonas WB, Ives J, Wijk RV, Weingartner O. Research on homeopathy: state of the art. J Altern Complement Med 2005;11:813—29.

Online supplementary material for: Witt, C, Bluth, M, Albrecht, H, Weißhuhn, TER, Willich, SN. The in Vitro Evidence for an Effect of High Homeopathic Potencies – A Systematic Review of the Literature. Complementary Therapies in Medicine 15 (2), 2007, pp. 128–138. Table 2: Reviewed Experiments
Publication Objective Technique Findings Merc-c and Sulf alternately inhibit and stimulate diastase until D60, Calc-m until D20. Inhibition of activity by Iris D6…D25, Aur-m D6; stimulation by Jab D6, Iod D6…D9. Stimulation alternates with inhibition or no effect until D45 (Ph-ac) or D100 (Iris). Ars D6 acts strongly stimulating, D15 inhibiting, no effects above D20, nor with Ins. Merc, Adren stimulate frog muscle enzymes; Adren effects show pseudosinusoidal curve with phases of activity and no effects until D40. No effects on bovine heart enzymes by Adren; only Coff and Glon inhibit until D15. Merc-c CC26…CC30 stimulates activity of diastase. Effect decreases with storage time, not found after 3 months. Substance Tested Control or Comparison Solvent of Potentizing Not declared

Non-Cellular Systems Persson and Influence of potencies on Photometry Ginsberg, 1932 the activity of malt diastase?

Persson, 1933

Influence of potencies on Photometry the activity of trypsinogen? Influence of potencies on the activity of glycogen reducing enzymes from a) frog muscle and b) bovine heart? Effect of high potencies of Merc-c on malt diastase activity? Affects storage duration potency activity? Do potencies of phosphor modulate a reaction involving phosphate group transfer by pyruvate kinase or luciferase? a) Effects of Bell on acetyle cholinesterase from goat brain? b) Effects of Ars on human serum cholinesterase?? Modification of a 50% inhibition of enzymes Photometry

Merc-c, Sulf D6…D60. Aur-m, Water Calc-m, Jab, Plat-m D6…D30. Iris, Nit-ac D6…D30. Bell, Benzac, Canth, Iod, Lyc, Ter, potency not stated Ars, Ins D3…D30. Ph-ac Water D6…D45. Iris D6…D100

Not declared

Persson, 1938

Boyd and Brit 1954

Photometry

Ars, Coff, Glon, Lac-ac, Merc-c Water Phos, Stroph, Stry-n D3…D30. Adren D3…D40. Adon, Ins, Natsal, Thyroxin (potency not stated) Merc-c CC26-30 ABD

Not declared

ABD

Kraus et al., 1981

Bioluminescen ce

Activity of pyruvate kinase stimulated (C5, C9, C13) or inhibited (C6, C14) by Phos. Luciferase not affected.

Phos C3…C15

ABD

Not declared

Jussal et al., 1984

a) Photometry, b) Comparison with standard curve Electrophoresi s; protein

a) Strong variability of activity. b) Ars ?27, ?28 inhibit activity.

a) Bell D1… D60. b) Ars ?27, ?28

a) 0-control b) EOH 10%

a) Not declared, b) EOH 10%

Petit et al., 1989

Arg-n, Cupr-s, Merc-c, Zinc-m D4 increase induced inhibition, higher potencies have no effect. No effects

Arg-n, Citrate, Cupr-s, Merc-c, molybdate, Phos, Zinc-m D4,

ABD

ABD

Publication

Objective (glucose-6 phospatase; NADPH-cytochrome-C reductase; galactosyl transferase; lactate dehydrogenase; 5'nukleotidase) by potencies of the inhibiting substance? a) Effect of D and C potencies of Merc-c on α-amylase from human saliva? b) Influence of pH? c) Effect of several remedies at different pH? Differences between potencies, dilutions, potency chords, and dilution chords regarding their effect on the activity of glutathione-S transferase (GST), acid phosphatase (AP) and xanthine oxidase?

Technique assays; Radioactivity determination

Findings from Phos, citrate and molybdate.

Substance Tested D6, C5, C7, C9, C11, C13, C15, C20, C30 except molybdate and citrate C30, except Phos D4, D6

Control or Comparison

Solvent of Potentizing

Shabir et al., 1996

Photometry

a) Amylase inhibited by Merc-c D1, D2, C1; higher potencies (D9…D15; C6…C12) stimulate activity. b) Results differ at different pH: All potencies stimulated at pH 7.0. At pH 4.5, 5.5, 8.5, both inhibition and stimulation occurred. c) Substances in C30 usually activated at pH 5.5, 7.0; and inhibited at pH 8.5. GST is inhibited by ubiquinone D8, D30, D200 and dilution chord D. SP inhibited by all preparations except ® Ubichinon-Injeel forte ; dilutions chord Df differs from ® D12, D30, D200 and Ubichinon-Injeel . Ubiquinone D8, ® D30, and Ubichinon-Injeel forte stimulate activity of xanthine oxidase. Multiple differences between single potencies and potency chords. Dilutions chord D differs ® from Ubichinon-Injeel .

a) Merc-c D1…D15. b) Merc-c C5, C10, C15, C20, C25. c) Acon, Ars, Bell, Graph, Led, Merc, Phyt, Puls, Sulf, Verat C30

Water

AD

Harisch and Dittmann, 1997

Photometry, comparison with standard curve

Ubiquinone D8, D12, D30, ® D200. Ubichinon-Injeel (=ubiquinone D12 + D30 + ® D200). Ubichinon-Injeel forte (=ubiquinone D8 + D12 + D30 + D200)

Harisch and Dittmann, 1998

Differences between potencies, dilutions, potency chords, and dilution chords of cAMP, regarding their effect on acid phosphatase (AP), glutathione-S transferase (GST), uricase, cAMPdependent proteine kinase (PKA)?

Photometry; HPLCanalysis; comparison with standard curve

Activity is inhibited (AP) or stimulated (uricase, PKA) by potencies and dilutions up to D200/dil200; GST not affected. Only difference between potencies and dilutions: D8/dil8 for uricase.

Water, Not declared chords of stepwise dilutions 1:10: 'Chord D' = ubiquinone dil12 + dil30 + dil200. ‘Chord Df' = ubiquinone dil8 + dil12 + dil30 + dil200 cAMP D4, D6, D8, D12, D30, Stepwise Not declared D200. cAMP D6 + D12 + D30 + dilutions 1:10: D200. cAMP D12 + D30 + D200 cAMP dil4, dil6, dil8, dil12, dil30, dil200. cAMP dil6 + dil12 + dil30 + dil200. cAMP dil12 + dil30 + dil200. Water

Publication Harisch and Dittmann, 1999 (cAMP)

Objective Differences in the effect on acid phosphatase between cAMP potency chords, their constituents, and controls? Differences in the effect on potato acid phosphatase between ubiquinone potency chords, their constituents, and controls? Influence of longer preincubation? Effect of variation of D8 amount in potency chord? Effect of potencies on uricase, acid phosphatase (AP), and glutathione-Stransferase (GST)? Effects of Merc-c, Merc-i C30 on α-amylase activity? Influence of storage duration (Merc-c only)? Effect of potencies on lipoperoxidation from homogenized rat brains compared to melatonin? Effect of HgCl2 potencies on activity of malt diastase and α-amylase?

Technique Photometry; comparison with standard curve

Findings All potency samples differ from Water. Some samples (potencies or potency chords) differ from others (no regularity). Potency chord effects always less inhibiting than sum of constitutent's effects.

Substance Tested cAMP D6, D12, D30, D200, also in combinations. cAMPa Injeel (= cAMP D12 + D30 + a D200). cAMP-Injeel forte (= cAMP D6+ D12 + D30 + D200) Ubiquinone D8, D12, D30, D200, also in combinations. ® Ubichinon-Injeel (=ubiquinone D12 + D30 + D200). Ubichinon® Injeel forte (=ubiquinone D8 + D12 + D30 + D200)

Control or Comparison Water

Solvent of Potentizing Not declared

Harisch and Dittmann, 1999 (Ubiquinone)

Photometry

All preparations inhibit activity. Ubichinon-Injeel forte inhibits more than all other preparations except D12. Effect of potency chords less than sum inhibition of components. After 40 min preincubation time, ® Ubichinon-Injeel decreases catalytic activity by 10%, ® Ubichinon-Injeel forte by 15%. Variation in D8 amount in potency chords influences results in a non-linear manner.

®

Water

Water

Dittmann et al., 2000

Photometry

Kali-cy D5, D6 inhibit uricase and AP; Kali-cy D8, D30 activate uricase. GST not affected.

Kali-cy D5, D6, D8, D30

Not declared

Not declared

Sukul et al., 2002

Photometry

Merc-c, Merc-i stimulate α-amylase in AD and EOH; Merc-c more than Merc-i. Effect of Merc-c C30 decreases with Storage time, not found after 1 month.

Merc-c, Merc-i C30 ultrasound potentized, 4, 30, 365 days old

AD, 'EOH 90%' C30 ultrasonicate d, 4, 30, 365 days old Melatonin 1M, 0.5M, 0.25M, 0.125M ABD; ABD C2…C30; HgCl2 dilutions 1:100: dil2… dil5

AD, EOH 90%

Batello, 2002

Photometry

Bluth, 2005

Photometry

Strongest inhibition with melatonin 1M and 0.5M. Ars C12, C30, Cupr C12, C30, and Mang C30 had moderate antiperoxidative effect compared to melatonin 0.125M. No difference between Merc-c potencies and succussed controls. Merc-c C2 inhibited α-amylase like the corresponding dilution, all higher potencies inactive.

Ars, Cupr, Mang, Zinc C6, C12, C30

Not declared

Merc-c C2…C30

ABD

Publication Cultured Cells Van Mansvelt and Amons, 1975

Objective

Technique

Findings

Substance Tested

Control or Comparison ABD

Solvent of Potentizing ABD

Aubin et al., 1980

Boiron et al., 1981

KandeferSzerszen et al., 1993

Delbancut, 1994

Does the growth inhibition of Merc-c on lymphoblast cells decrease to zero with increasing potency? Can the regeneration of in vivo CCl4 induced rat liver cell necrosis be modified in vitro by Phos (as globules, dilutions)? Do potencies of Merc-c have a protective effect on fibroblasts exposed to HgCl2? Effect of interferon-α on tumor cell (A549) growth? Differences between D and C potencies? Exactly reproducible? Effect of heating initial interferon stock preparation? Effect of interferon-α potencies on tumor cell (A549) antiviral activity against vesicular stomatitis virus? a) Prophylaxis for pig kidney cells (LLCPK1) against intoxication by pretreatment with the potentized noxa (Cadmmet, Cisplat)? b) Does Preincubation with Cadm-met potencies for 120 h influence growth? c) Optimal preincubation time for maximum

Coulter Cell Counter

Merc-c D5, D6 inhibit cell growth. Weak replicated inhibition with D16, D17.

Merc-c D5…D25

Microscopy

Globules deteriorate, dilutions improve cellular regeneration compared to controls.

Phos C7, C15

a) NaCl 0.9%. b) Placebo globules 'ABD', potency not stated

Not declared

Microscopy

Pretreatment with Merc-c C5 increases mitotic index by Merc-c C5, C15 ca. 10% compared to controls; C15 is ineffective.

Not declared

Microscopy; photometry

Pseudosinusoidal stimulation-inhibition curve of cell growth, regular peaks/lows every 6…9 D potencies; similarly with C potencies. Every line of potentizing shifts peak/low location (no exact replications). More similar results when using the same potencies in intervals of one week. Potencies show no activity if initial solution is heated. No influence of interferon potencies on antiviral activity.

Medium Interferon-α D1…D40, C1…C40 Interferon-α dilution in medium. 'Medium' D80

Photometry; spectrometry; microscopy

a), c) Protective effect of Cadm-met C10 after 120 h Cadm-met, Cisplat C5, C10, but not after 48h preincubation. Strong protective effect C15, C20 after 120 h against Cadm-met in other high potencies up to C20. b) Preincubation with Cadm-met potencies alone has no influence on growth. d) Prophylactic effect increases with potency. e) Only low Cadm-met -5 doses (up to 3x10 M) can be countered. f) Against Cisplat, Cadm-met C20 increases mortality by 6%. g) With Cadm-met pretreated cells was found: less degeneration of cytoskeleton; less Cadm-met penetration into the cell (for low intoxication

'Medium' C5, C10, C15, C20

Medium

Publication

Objective

Technique

Findings concentrations); increased expression of (protective) metallothioneine, but decreased (more with higher potencies) when cells are incubated in presence of Cadm-met or Cisplat potencies without intoxication. h) Potentizing with EDTA prevents protection by Cadm-m C15 and increases mortality in only pretreated cells. i) Cycloheximide raises cell mortality of Cadm-m C15 pretreated cells after intoxication.

Substance Tested

Control or Comparison

Solvent of Potentizing

Pison et al., 1995

protection? d) Differences between potencies? e) Maximum preventable intoxication dose? f) Crossover protection between Cadm-met and Cisplat? g) What cellular mechanisms are triggered? h) Does a chelator (EDTA) affect the Cadm-met potency when added in potentizing? i) Are potencies effective in presence of a protein biosynthesis inhibitor (cycloheximide)? Proliferation of Photometry fibroblasts affected by high potencies? Potentized EOH different from unpotentized? Effect of homeopathic remedies in various pharmaceutical forms, in potencies or dilutions on cell cultures (EBL; HeLa; MDBK cells)? Prophylactic or curative effect of potencies against intoxication with their stock preparation? Effect of high potencies of TNF-α on H2O2production of neuroblastoma cells? Photometry; microscopy

All investigated potencies including potentized potentizing solvents (EOH, lactose) inhibit growth similarly, differently from unpotentized EOH.

Bell, Thuj D8, D12, C30, C200, C1000

Then, 1995

Inhibition of cell growth by Ars up to D6, no difference to corresponding mixtures. Blends and triturations with lactose different for Ars D4, Merc-c D12. Prevention only found for Ars D7; no curative effects.

Ars, Cupr-s, Merc-c D3…D10, D12, D15, D18, D24, D30, D200. Thuj D2…D6, D8, D12, D30

EOH 43%, ‘EOH 43%’ C30, lactose, cell culture medium, buffer ABD. EOH 70%. Lactose -4 -8 10 , 10 , -12 -15 10 , 10 , -18 10

EOH 43%, lactose (trituration)

ABD. EOH 70%. Lactose, medium

Carmine, 1997

Chemolumines D100 stimulates H2O2-production by +19%…199%. cence Stimulation shows an oscillating curve (somewhat pseudosinusoidal) against potency, rising with higher potencies. Potentized ABD also increases H2O2-

TNF-α D1…D100

AAI. ‘AAI’ D30, D70, D100

AAI

Publication

Objective Biological effects of potentized Water compared to unpotentized? Influence on cell-free reaction? Action of potencies on cell cultures of 1) neuroblastoma and human melanoma cells, 2) stimulated human leucozytes, 3) alveolar type II-cells from rat lungs?

Technique

Findings production. The biochemical reaction itself remains unchanged in presence of potencies.

Substance Tested

Control or Comparison

Solvent of Potentizing

Herberth and Pison, 1998

1) Enhanced chemolumines cence; 2) luminolchemolumines cence; 3) γradiation of 14 C-choline; protein and phospholipid concentration Photometry; fluorometry

1) TNF-α potencies did not influence chemoluminescence. 2) No potency altered the chemoluminescence of stimulated or resting leucozytes. 3) Inclusion of choline in phospholipid and protein production not influenced by tested preparations.

1) TNF-α D10…D100; Zymosan. 2) Zymosan D10…D100; Bell Ø, D8, C12…C1000; Ferr-p, Thuj, potency not stated. 3) Bell, Colch, Lec, potency not stated

Jonas et al., 2001

Marotta et al., 2002

Neuroprotective effects of potentized glutamate for various neuron samples (of cerebral, cerebellar, spinal origin) against toxic doses of glutamate? Is the effect 2+ due to a decreased Ca influx? Protection of neuronal cells pretreated with potencies of the neurotoxins cycloheximide, NMDA or MPP-iodide against excitotoxic glutamate concentrations? Influence of potencies on erythrocyte aquaporins from Clarus batrachus, with and without prior ethanol intoxication?

Weak cell-type specific neuroprotective effect (mortality Glutamate C9…C15 ca. -10%) in some potencies in somewhat sinusoidal curve against potency, peak locations vary with cell type. With higher glutamate concentrations only the highest potency (C15) increased survival. Intracellular 2+ Ca influx in spinal neurons not affected by glutamate C9, C11.

1) TNF-α 10 10 -100 , 10 ; buffer. 2) Zymosan 0.5mg/ml, 10 10 -100 , 10 , 10 1000 ; AD; EOH 43%; buffer; saccharose. 3) Not declared 'Water + EOH 95% + Glycerol' C9…C15

-

EOH 43%

Water + EOH 95% + Glycerol

Photometry

Cycloheximide C2 decreased neuronal survival by 18%, cycloheximide C13 increased it by 5%. All other tested potencies had no effect. Except Ca, K, Na, Si, 29 tested elements present only in negligible quantity, similar concentrations in controls.

Cycloheximide C2…C5, C13, Water C31; NMDA C3…C6, C14, C32; succussed MPP iodide C3…C6, C14, C32 120 times

Deionized sterile filtered water

Erythrocytes Sukul et al., 2003

Erythrocyte weight loss from drying after hypotonic incubation

Water permeation was enhanced with Merc-c and Nux- Nux-v, Merc-c C30 (sonicated) v C30 compared to water controls. No reduction compared to ethanol intoxicated erythrocytes.

EOH C30; water; nullcontrol

EOH 90%

Publication

Objective

Technique

Findings

Substance Tested

Control or Comparison NaCl 0.9% with dissolved lactose globules NaCl 0.9%

Solvent of Potentizing NaCl 0.9% with dissolved lactose globules NaCl 0.9%

Basophile Granulocytes Murrieta et al., Antigen (mite) triggered 1985 degranulation of basophiles from allergic probands inhibited by Apis potencies? Poitevin et al., Antigen (mite) triggered 1985 degranulation of basophiles from allergic probands modified by Apis potencies? Sainte-Laudy 1) Effects of Histamine, and Belon, platelet activating factor 1986 (PAF), and lyso-PAF on degranulation of basophiles from allergic probands? 2) Influence of incubation time on PAF, lyso-PAF effects? 3) Influences of thermal treatment on potency effects? 4) Affect Histamine potencies the half maximum degranulation antigen dose? Belon, 1987 a) Effect of Histamine on D. pteronyssinus induced degranulation of basophiles from a sensitized proband? b) Can the effect of Histamine C6, C17 be reproduced for different allergen concentrations with basophiles from 30 house dust allergy patients?

Microscopy

No inhibition of degranulation found.

Apis C5, C9, C15, C30

Microscopy

Degranulation increased with Apis C5 by +20%, decreased by C9, C15 by -60%.

Apis C5, C9, C15

Microscopy

1) Effect peaks of Hist at C6, C7 and C16…C18; ineffective potencies in between (C10…C15). Maximum effects at C9, C10 for PAF and lyso-PAF. 2) Effect rises with incubation time; slower but to same dimension after 30 min with lyso-PAF. 3) Boiling destroys efficacy of Hist C7, PAF C10, C11, and lysoPAF C9…C11. Repeated deep-freezing decreases effects. 4) Different potencies show different degranulation-antigen curves.

Hist C5…C20. PAF, lyso-PAF C6…C15

Buffer. ‘AD’ C18

Not declared

Microscopy

a) Degranulation inhibited by some potencies, maxima at C6, C17. b) Marked inhibition by C6, C17 with at least 2 antigen concentrations for most probands. Effects stronger with lower antigen concentration.

Hist C1…C24

AD

Not declared

Publication Davenas et al., 1988

Objective

Technique Microscopy

Findings a) Degranulation triggered by potentized anti-IgE, not by anti-IgG. b) Potencies made with dimethylsulfoxide ineffective. Heating, freezing and sonication decrease efficacy.

Substance Tested Anti-IgE D1…D60, C1…C60. Anti-IgG C1…C60

a) Do high potencies of anti-IgE or anti-IgG induce degranulation of human basophiles? b) Influences of solvent, heating, deep freezing or sonication? Metzger and Do potencies of anti-IgE Dreskin, 1988 or dinitrophenyl induce degranulation of leucaemic rat basophiles? Poitevin et al., a) Do potentized lung 1988 histamine or Apis inhibit -9 anti-IgE induced (10 M) degranulation of human basophiles ? b) Do potencies of anti-IgE trigger degranulation that can be inhibited by potencies of lung histamine and Apis? c) Direct effect of potencies? Ruff et al., 1988 Inhibition of antigen induced degranulation of basophiles from allergic probands whole blood by potencies of pollen, Histamine, Ars? Sainte-Laudy, Effect on antigen 1989 induced degranulation of (Methylhistamin basophiles from allergic e part) probands whole blood by potencies of 4-methylhistamine? Benveniste et Do high potencies of al., 1991 Apis inhibit anti-IgE and anti-IgG induced

Control or Comparison Buffer. AntiIgE dilutions -1 -60 10 …10

Solvent of Potentizing Buffer. dimethylsulfo xide

Autoradiograp hy

No effects of high potencies of allergen or antibodies.

Anti-IgE, dinitrophenyl-albumine Buffer D5…D35

Not declared

Microscopy

a) Lung histamine C1, C9 increase, C5, C15 and Apis C8, C9, C10 inhibit degranulation induced by anti-IgE. b) Anti-IgE D16, D17, D18 induce degranulation that can be inhibited by potentized lung histamine or Apis. c) Without prior activation from anti-IgE, Apis and lung histamine do not affect degranulation.

Lung histamine, Apis C1…C20. Anti-IgE D16…D22

NaCl (concentratio n not stated) + 65% EOH for C1, C1…C20

NaCl (concentratio n not stated) + 65% EOH for C1

Fluorometry

Only Ars inhibits degranulation triggered by grass pollen. Hist shows a tendency to inhibit. Dust mite antigen triggered degranulation not modified by the tested potencies.

Ars C15. Hist C7. Pollen C9

Buffer

AAI

Microscopy

Inhibition by 4-methyl-histamine at C6, C16.

4-Methyl-histamine C4...C19, prepared in polystyrene tubes or glass flask

Allergene free

Water

Microscopy

Degranulation was found for anti-IgE and anti IgG that is not induced by controls. Apis C30, C32, C34, C40 inhibit anti-IgE induced degranulation, potentized

a) Anti-IgE, anti-IgG D21…D30. b) Apis C30…C40

a) 'ABD' a) buffer. b) D21…D30. b) NaCl 'NaCl' (concentratio

Publication

Objective degranulation of human basophiles?

Technique

Findings solvent does not.

Substance Tested

Sainte-Laudy et Do potencies of al., 1991 Histamine, Histidine modify degranulation of basophiles from probands being allergic to dust mite? Effects of adding cimetidine or histaminase to the potencies? Sainte-Laudy Do potencies of and Belon, Histamine inhibit anti-IgE 1991 induced degranulation of human basophiles? Influence of variations in protocol (concentrations of anti-IgE, number of controls, reproductions)? Ovelgönne et Do high potencies of al., 1992 anti-IgE induce degranulation of human basophiles? Hirst et al., Do potencies of anti-IgE 1993 induce degranulation of human basophiles?

Microscopy

Maximum inhibition of degranulation for Hist found at C6, C16, C26, C39, C51; no effects for Histid. Cimetidine suppresses the Hist effects (C4…C19). Histaminase prevents effects of Hist C6,C7, but not of Hist C16, C17.

Hist C4…C57. Histid C4…C19

Control or Comparison (concentratio n not stated) D40 Allergene free control

Solvent of Potentizing n not stated)

Water

Microscopy

Higher potencies (Hist C15…C18) are effective with low (0.2 µl/ml) but not for higher (1, 5.0 µl/ml) concentrations of anti-IgE.

Hist C6, C7, C15…C18

'ABD' C15…C18

ABD

Microscopy

No difference between potencies of anti-IgE and diluted controls.

Anti-IgE D21…D30

Anti-IgE 10 2 -30 …10

-

buffer

Microscopy

Sainte-Laudy and Belon, 1993

Do potencies of Microscopy Histamine inhibit anti-IgE induced degranulation of human basophiles?

No significant reproducible effect of potencies >C2. Succussed IgE, unsuccussed IgE and succussed buffer apparently different. High buffer potencies showed linear correlation of degranulation and potency. Inhibition of anti-IgE induced degranulation by Hist C10…C38, most frequently by C9, C10, C16.

Anti-IgE C2…C30

'Buffer' C2…C30. Anti-IgE 10 2 -30 …10 Water. AntiIgE free control

buffer

Hist C6…C18

ABD

Sainte-Laudy and Belon,

Do potencies of Histamine inhibit

Flow cytometry Inhibition of CD63 expression by Hist C1, C2, C11, C17. No change in fluorescence density, nor in

Hist C1…C20

0-Controls. Anti-IgE free

AD

Publication 1996

Objective

Technique

Findings percentage of anti-IgE+ cells (except Hist C2).

Substance Tested

expression of markers related to degranulation in anti-IgE activated human basophiles? Sainte-Laudy Do potencies of and Belon, Histamine inhibit 1997 expression of CD63 in anti-IgE activated human basophiles? Also in presence of cimetidine? Belon et al., Do potencies of 1999 Histamine inhibit anti-IgE induced degranulation of human basophiles? Brown and Do potencies of Ennis, 2001 Histamine inhibit anti-IgE induced CD63 expression in basophiles? Effect of heating or repeated deep freezing? Sainte-Laudy, Do potencies of Histidine 2001 or Histamine increase anti-IgE induced expression of human basophil CD63? Effect of cimetidine? Lorenz et al., Effects of potentized 2003 (Solvents) Histamine on CD63 expression in anti-IgE activated basophiles from human responders? Effects of different potentizing solvents? Lorenz et al., Influence of various 2003 protocols on Histamine (Protocols) potency induced CD63expression of anti-IgE activated basophiles

Control or Comparison controls

Solvent of Potentizing

Flow cytometry Hist C15, C16, C17 inhibit anti-IgE induced CD63 expression slightly (-1.4%…3.6%) compared to presence of cimetidine.

Hist C10…C20

Cimetidine. Anti-IgE free controls

AD

Microscopy

Minor significant inhibition of anti-IgE induced degranulation by high potencies of Hist in 3 of 4 participating laboratories (p=0.065 for the fourth).

Hist C15…C19

'AD' C15…C19

AD

Flow cytometry Hist C1, C2, C3, C7, C9, C10, C13 inhibit expression of Hist 10 M…10 M (title says CD63; maximum with C10 (-43.8%). Activity decreased “homeopathic concentration”, by heating, unaffected by freezing the potencies. paper uses “dilution” terminology and units)

-2

-40

Isotype matched nonspecific antibodies

Not declared

Flow cytometry Hist C13 increases expression of CD63 (+42%) and activated cell percentage, while Hist C14 does not. Cimetidine diminishes this activation. Histid C13 not different from potentized AD.

Hist C13, C14. Histid C13

'AD' C13, C14

AD

Flow cytometry Solvent a) potencies of Hist inhibit CD63 activation in Hist D2…D30 made in a) EOH 4.8% and stimulate in 22.6% of the experiments, + ABD + buffer, or b) brandy + 72.6% do not differ from controls. Solvent b) potencies ABD + buffer inhibit in 57.1% of experiments, 42.9% do not differ from controls. Solvents differ clearly in their inhibition at D10…D30, varying with probands. Flow cytometry Basophile count varies (0.6-3.6%), optimal activation at Hist D2…D34 prepared in 0.6µg/ml anti-IgE (final concentration); still ≥20% antiglass, polystyrene, or IgE nonresponders must be excluded. Variance polypropylene decreases with increasing basophile count, therefore 10.000 cells per preparation are necessary; variance is

Hist D2. Solvent a). Solvent b)

a) EOH + AD + buffer. b) brandy + AD + buffer

Hist D2. Medium

AD. Solvent A. Solvent B (solvents not specified)

Publication

Objective from responder probands?

Technique

Findings lower in polypropylene containers than in polystyrene. Activation is stable for 2 days. In this optimized test system Hist D1…D10 and D21…D25 inhibits CD63 expression of anti-IgE (0.5µg/ml) activated basophiles. #2) Histamine dilutions C14–C18 inhibited degranulation in laboratory 4, only three potencies (C1, C2, C10) were active in lahboratory 3. In laboratory 1 Histamine dilutions C15–C18 were different from controls. #3A) Histamine release was inhibited by all tested potencies. #3B) Ranitidine 10–4M and cimetidine 10–5M reduced the histamine induced inhibition for three of four tested potencies. Cimetidine 10–5M inhibited activation for Histamine C16 in a second experiment. #3C) Histamine C16 inhibited basophil activation. Histidine C16 potency was not active

Substance Tested

Control or Comparison

Solvent of Potentizing

Belon et al., 2004 (#2-#3)

Guggisberg et al., 2005

#2) Multicenter-study in 3 laboratories concerning the reproducability of the action of histamine on IgE-activated basophiles. #3A) Measurement of basophil activation due to histamine dilutions by means of histamine release. #3B) Modulation of histamine effect on basophil activation by H2-receptor antagonists? #3C) Comparison of Histidine to Histamine dilutions Effect of histamine potencies on anti-IgE induced degranulation? Influence of variations of protocol?

#2) Flow cytometry. #3A) Fluorimetrical measurement of histamine in supernatant and in cells. #3B) Flow cytometry. #3C) Flow cytometry

#2) Histamine C14–C18, C2C20 and C15-C19 #3A) Histamine C5-C20. #3B) Histamine C14-C17. #3C) Histamine C16, Histidine C16

#2) Anti-IgE #3A) not stated. #3B) Anti-IgE. #3C) water

#2) AD #3A) AD. #3B) AD. #3C) AD

Flow cytometry Histamine C1, C11 inhibited CD63 expression. Against all controls pooled only C1 was significantly inhibiting. Results were influenced by position on microtiter plate, by storage and incubation times of potencies. Neither use of polystyrene tubes, cell culture plates or microtiter plates affected degranulation, nor did dextrane sedimentation. Microscopy Form-ac D3 stimulated phagocytosis, higher potencies ineffective.

Histamine C1…C17

ABD C1…C17

AD

Neutrophile Granulocytes Fanselow, 1984 Effect of form-ac potencies on phagocytosis rate of human neutrophiles? Chirumbolo et Do potencies influence al., 1993 the stimulated superoxide production or adhesion of human neutrophiles?

Form-ac D3, D6, D30.

NaCl

Not declared

Photometry

Low potencies act up to D6; high potencies only in three cases (Mag-p D30, D60; Phos D30). Experiments with Phos D6…D200 show individual variations according to test subjects.

Alpha-ketoglutaric acid, Aconac, Cit-ac, Fuma-ac, Mag-p, Mal-ac, Mang-p, Phos, Sulf in 6…13 potencies from D2 to D600.

NaCl 0.9%

NaCl 0.9%

Publication Lymphocytes Bildet et al., 1984

Objective

Technique

Findings

Substance Tested

Control or Comparison NaCl 0.9%. 0-Control

Solvent of Potentizing Not declared

Colas et al., 1984

Effects of Phyt on PHA stimulated proliferation of human whole blood lymphocytes? Influence of variations in PHA dose, potency dose and application mode? Effect of Phyt on proliferation of rabbit lymphocytes ? Influence of PHA stimulation? Reaction of whole blood lymphocytes from healthy, allergic or immune suppressed probands to PHA stimulation and incubation with Phos or Apis? Does potentized house dust influence migration of leucocytes from allergic probands?

Microscopy

From 3 protocols only maximum PHA stimulation yields Phyt C7, C15 a significant result: Phyt C7 inhibits proliferation if applied 15 min before or after PHA. Higher effects when applying potency before PHA than vice versa.

Lymphocyte transformation test

Chirila et al., 1992

Lymphocyte transformation test

Phyt C5…C15 ineffective on unstimulated Phyt C5, C7, C9, C15 lymphocytes. Proliferation diminished in PHA stimulated cells by the highest potency (C15) by 28%…73%. Higher potencies more effective than lower. Lymphocyte proliferation of healthy and allergic Apis, Phos C7, C15, C30 probands inhibited by Apis, Phos; higher potencies (C30) more effective. Immune suppressed lymphocytes react weakly to PHA, here no effects of potencies.

Not declared

NaCl 0.9%? ("9% physiologique ") ATD

Succussed ATD

Gibson and Gibson, 1996

Microscopy

C4…C13, C18, C27, C50, C200, C300, C400, C500, C1000 with abnormal migration; no effect of C14, C15, C20, C22, C25, C30, C100.

House dust in 25 potencies from C4 to C1000

EOH 20%

EOH 20%

If a publication listed above presented several experiments (1-5) these were scored individually (Table 3). AD = aqua destillata, ABD = aqua bidestillata, ATD = aqua tridestillata, AAI = aqua ad iniectione; EOH = ethanol. “Not declared” includes unspecific descriptions like “according to national pharmacopea”. Substances known as homeopathic remedies are listed with common abbreviations (6). Dn, Cn = decimal, centesimal potency of n potentizing steps, CCn = potentized with 1:200 dilution; diln = stepwise dilution (not succussed); 10-n = single-step dilution; Ø = unpotentized; ?n = dilution ratio of potentizing not stated. a Heel GmbH, D-Baden-Baden; not commercially available.
References 1 Jussal, RL, Dua, RD, Mishra, RK, Meera, S, Agarwal, A. Effect of Ultradilutions on Neurotransmitter/Enzyme. Hahnemann Gleanings 1984;51:245-250. 2 Herberth, G, Pison, U. Homöopathische Arzneimittel in zellbiologischen Systemen [Homeopathic Remedies in Cellbiological Systems]. In: Albrecht, H, Frühwald, M, editors. Jahrbuch der Karl und Veronica Carstens-Stiftung, Band 5 (1998). Essen: KVC; 1999. pp. 77-95. 3 Sainte-Laudy, J, Belon, P. Application de modèles d`hypersensibilité du type I à l'étude de l'activité de dilutions hahnemanniennes des médiateurs de cette hypersensibilité [Application of hypersensitivity type I models on the study of the activity of Hahnemannian dilutions of mediators of this hypersensitivity]. Homéopathie 1986;3:40-44. 4 Belon, P, Cumps, J, Ennis, M et al. Histamine dilutions modulate basophil activation. Inflamm res 2004;53:181-188. 5 Sukul, NC, De, A, Sinhababu, SP, Sukul, A. Potentized Mercuric chloride and Nux vomica Facilitate Water Permeability in Erythrocytes of a Fresh-Water Catfish Clarius batrachus Under Acute Ethanol Intoxication. J Altern Complement Med 2003;9:719-725. 6 Schroyens, F. Synthesis: Repertorium homoeopathicum syntheticum. Greifenberg: Hahnemann Institut für homöopathische Dokumentation; 1993.

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