No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Replication of an experiment on extremely diluted thyroxine and highland amphibians
Abstract
The purpose of this study was to reproduce an experiment with diluted thyroxine and amphibians. A detailed account of the difficulties of this line of research has been published by the initial team (Endler and Scherer-Pongratz). One experiment which has been reported reproducible by the initial team and independent researchers is the effect of extremely diluted agitated thyroxine (T30x) versus analogously prepared water (W30x) in amphibians from biotopes above the tree line (highland amphibians).
(A) The author replicated the experiment. Rana temporaria were taken from an alpine biotope and the methods given in the original protocols were followed. Animals were treated from the 2-legged stage on. (B), the author reanalyzed the results reported by the initial team and by independent researchers (van Wijk, Lassnig, Zausner-Lukitsch, Bach, Harrer).
(A) In the author's own experiment, there was a clear trend of T30x animals developing more slowly (i.e. up to 6 h within 3 days) than W30x animals. This is in line with the previous experiments. Due to small numbers of animals, the differences in the frequency of larvae reaching the 4-legged stage and the stage with reduced tail were not statistically significant (p > 0.05). The effect size was large (d > 0.08). (B) In the analysis of all available data with regard to the 4-legged stage, pooled T30x values from the initial team were 10.1% smaller than W30x values (100%) and pooled T30x values from the 5 independent researchers were 12.4% smaller (p < 0.01 and d > 0.08). Analogously, the number of animals entering the juvenile stage with reduced tail was smaller for T30x than for W30x.
... According to a study conducted by Harrer, 48 hourly applications of Thyroxine 30D have an inhibitory effect on the morphogenesis of highland amphibians [4]. The purpose of Harrer's study was to reproduce an experiment conducted by Endler et al. using diluted Thyroxine on amphibians [5]. ...
... The Thyroxine 30D and the Water 30D test solutions were prepared in a similar manner by successive succussions and dilutions [4]. The results of Harrer's study (2013) were in line with that of Endler's study; there was a clear inhibitory trend on both parameters. ...
... The specific species Xenopus laevis was chosen as it is considered of "least concern" on the IUCN Red List of Threatened Species with an increasing population trend [7]. To date, most of the research available involving the topic of amphibians, ultrahigh dilutions of thyroxine and homeopathy have been conducted using 30D potencies and although the exact results have varied, they have all shown an inhibitory trend on metamorphosis [2][3][4][5]. ...
... Quality of life was found to be better in the group receiving homeopathic treatment. Further studies in oncology revealed a high level of treatment satisfaction in the case of complementary homeopathic treatment (22) and a decrease in symptoms of oestrogen withdrawal in female patients with breast cancer under complementary homeopathic treatment (23). In a recent randomised pragmatic trial in Austria cancer patients were randomly assigned to receive either conventional therapy or conventional therapy plus homeopathic treatment (24). ...
... In the light of the relevant global meta-analyses of homeopathy published to date it is clear, on the whole, that in four out of five cases potentised medicines tend to reveal specific efficacy in excess of placebo. The overall outcome is only negative (homeopathy = placebo) if a large amount (90%-95%) 23 of the available data is excluded from the analysis and/or dubious statistical methods are employed. In each of these cases measures are used that deviate from the usual scientific standards insofar as the desired increase in reliable data, by excluding studies with certain features, is not reasonably in proportion with the accepted narrowing of the database (for example, a dropout rate of <10% = 9 studies versus <5% = 5 studies; see above). ...
... 24 20 Higgins & Altman (2011) 21 Mathie et al. (2014) 22 Ibid. 23 Cf. Hahn (2013) 24 Cf. ...
This report on the current state of homeopathic research provides a summary on the research areas of healthcare research, randomised controlled clinical trials, meta-analyses and basic research. It aims to contribute to the discussion within the field of homeopathy concerning the need for research, the relevance of individual research fields and methods and their role in future research strategies.
A summary analysis of the clinical research data offers sufficient evidence of the therapeutic effectiveness of homeopathic treatment. The results from numerous placebo-controlled trials and basic research experiments suggest, moreover, that potentised medicines offer specific efficacy.
Put in perspective, there are many important open research areas – notably: Basic research into the optimisation of laboratory models and the understanding of the mode of action, Independent replications of studies in clinical and basic research, Exploration of the provision of homeopathic care in reality, also combined with conventional medicine and Health economic analyses to evaluate the costs and benefits (cost effectiveness).
... The authors compared the results of the initial researcher 12 and a second researcher 12 as well as of external researchers. [13][14][15][16][17] They scrutinized reproducibility, and tried to determine the influence of external factors on the experimental outcome. Their hypothesis was that results would prove similar across the categories defined and that factors determining the outcome could be identified. ...
... 4,29 4. T30x sealed in glass vials and applied during a few minutes, on climbing activity, showing animals to be less active than control (p<0.01) 5. T30x directly applied to the basin water at intervals of 8 hours (short interval treatment), showing animals to develop faster than control (p<0.01) Study 1 1 was repeated [13][14][15][16][17] several times in the years after 1994, as discussed in this paper. Replications of study 2 produced the same result (information from T30x sealed in glass vials yielding slower development than control) in the hands of the initial researcher (A) (trend, p>0.05), the second centre (B) (p<0.01), an independent researcher (C 1 ) in the Graz laboratory (trend, p>0.05), a researcher (C 2 ) , in Turin (trend, p>0.05), and two researchers (C 3 and C 4 ) in Vienna (trend in both cases, p>0.05), but no differences between groups in the hands of a further independent researcher (C 5 ) in the Graz laboratory (p>0.05). ...
Background:
A model of thyroxine and metamorphosis of highland amphibians is frequently mentioned as an example of experiments on extremely diluted substances in discussions around 'homeopathy'.
Methods:
The model was scrutinized by reanalysing the results of the initial researcher A and a second researcher B as well as of 5 external researchers C between 1990 and 2013. Rana temporaria larvae were taken from an alpine highland biotope. The test solution was thyroxine 10(-30) (T30x), tetra-iodo-thyronine sodium pentahydrate diluted with pure water in 26 steps of 1:10, being agitated after each step. Analogously prepared water (W30x) was used for control. Tadpoles were observed from the 2-legged to the 4-legged stage. Experiments were performed in different years, at different times of season, and their duration could vary. Frequencies of 4-legged animals, effect sizes and areas under the curves (AUCs) were calculated and regression analyses were performed to investigate possible correlations between year, season, duration etc. Experiments were in line with animal protection guidelines.
Results:
The total set of data A + B + C as well as subsets A (initial researcher, N=286+293), B (second centre, 965 + 965) and C (5 external researchers, 690 + 690) showed an effect of extremely diluted agitated thyroxine reverse to that known of molecular thyroxin, i.e. test values were below control by 11.4% for A, 9.5% for B and 7.0% for C (p<0.001 for each of the subsets). The effect size (Cohen's d) was >0.8 (large) for both A and B and 0.74 (medium) for C.
Conclusion:
Although a perfect reproducibility was not obtained, this paradoxical phenomenon was generally consistent in different observations. Correlations were found between details of laboratory handling, as well as environment temperature, and the size of the results.
... In the course of more than two decades of experimental work on a model with amphibians and extremely diluted thyroxine, one experiment in particular, investigating the effect of an ultra-high dilution of thyroxine (T30x) v analogously prepared water (W30x) in amphibians from highland biotopes, was found to be reproducible. A total of 22 experimental runs were performed between 1990 and 2011, 15 by the initial researchers and 7 by altogether 5 independent researchers (Endler et al. 1991, Zausner et al. 2002, Interuniversitäres Kolleg 2010, Harrer 2013. ...
... Animals were transferred from their highland habitats (where temperature was 15-17°C) to the respective laboratories (19-27°C) at room (car-, train-, respectively) temperature; only in one case (Harrer 2013), they were stored at 4°C for several days prior to the experiment. Cooling here seemed to be a promising means of facilitating the transport of the highland larvae to laboratories and of synchronizing the start of experimental work. ...
SHORT COMMUNICATION Introduction In the course of more than two decades of experimental work on a model with amphibians and extremely diluted thyroxine, one experiment in particular, investigating the effect of an ultra-high dilution of thyroxine (T30x) v analogously prepared water (W30x) in amphibians from highland biotopes, was found to be reproducible. A total of 22 experimental runs were performed between 1990 and 2011, 15 by the initial researchers and 7 by altogether 5 independent researchers (Endler et al. 1991, Zausner et al. 2002, Interuniversitäres Kolleg 2010, Harrer 2013). In most of these (the sole exception being two performed and reported by the initial team) a trend was found of T30x-animals developing more slowly than W30x-animals. Pooled T30x values obtained by the initial team were 10.1% lower than W30x values (100%) (p < 0.01), and pooled T30x values from the 5 independent researchers were 12.4% lower (p < 0.01). Animals were transferred from their highland habitats (where temperature was 15-17°C) to the respective laboratories (19-27°C) at room (car-, train-, respectively) temperature; only in one case (Harrer 2013), they were stored at 4°C for several days prior to the experiment. Cooling here seemed to be a promising means of facilitating the transport of the highland larvae to laboratories and of synchronizing the start of experimental work. The purpose of this study was to test the hypothesis that storage of the animals at 4°C for several days prior to the experiment does not influence (i.e. inhibit) the effect of T30x on metamorphosis.
... Along more than 20 years, starting in 1991, Endler et al. performed countless multicentre tests with many variations of the core model parameters to test the hypothesis that non-molecular information is transferred in living systems (Endler et al., 1991;Oberbaum, 2013). In addition to demonstrating that high-diluted thyroxin (30x) slows down the thyroxin-regulated metamorphosis of Rana temporaria, they succeeded in designing a highly reproducible model (Endler et al., 2010;Harrer, 2013). Guedes et al. (2004Guedes et al. ( , 2010Guedes et al. ( , 2011 (Yaoita & Nakajima, 1997). ...
... Según Brito Abreu F,14 la homeopatía funciona desde hace más de un siglo, se aplica en animales con un éxito rotundo, los cuáles suelen ser muy poco sugestionables, sobre todo si padecen de alguna dolencia. Uno de los estudios que apoyan dicha afirmación es el realizado por Harrer B,15 donde a un grupo de ranas se le aplicó concentraciones homeopáticas de tiroxina a 10 CH, mientras al otro grupo se le empleó agua. Hubo mayores transformaciones en el estado de maduración en el grupo que usó homeopatía. ...
Background: homeopathy is a therapeutic system where organic, mineral, or vegetal substances are administrated which can produce the same symptoms in healthy person that the disease to treat.
Objective: to analyze the backgrounds of homeopathy, some research that try to demonstrate its effectiveness and the main ideas of the detractors of this theory.
Methods: this bibliographic review was conducted through search Scholar Google by typing these words: homeopathy, homeopathy remedies and water´s memory. Thirty original articles and 15 bibliographic reviews were chosen for the word homeopathy; 26 original articles and 12 bibliographic reviews for the combination of words homeopathy remedies, as well as 30 original articles and 10 bibliographic reviews for the combination of words water´s memory. Those 123 references were analyzed to check the ones that would be useful for the achievement of the article’s objective, choosing those that appear as bibliographical references.
Development: the theory of homeopathy, the diseases’ causes and the way to prepare homeopathic medicine are tackled. Also some research about homeopathy in the world is analyzed, where the existence of favorable results to homeopathic products can be noticed. Besides, possible mechanisms of action of homeopathy are explained and some reasons for which some people are septic with homeopathic medicine are showed.
Conclusions: Research about homeopathy must continue.
DeCS:HOMEOPATHY; MEDICAMENTOUS DISEASE IN HOMEOPATHY; HOMEOPATHY BROADCASTING; VITAL FORCE IN HOMEOPATHY; REVIEW LITERATURE AS TOPIC.
... On going through the list of researchers whose replication research has at times produced zero effects one will incidentally also come across ones who can absolutely be counted among the homeopathy research community (Table 1). Another example is one external researcher who first found a comparable effect 65 and then, after joining the initial laboratory's team and, after changing a crucial laboratory parameter for exploratory purposes (i.e. temperature), a zero effect. ...
Introduction: This paper focuses exclusively on experimental models with ultra high dilutions (i.e. beyond 10e-23) that have been submitted to replication scrutiny. It updates previous surveys, considers suggestions made by the research community and compares the state of replication in 1994 with that in 2015.
Methods: Following literature research, biochemical, immunological, botanical, cell biological and zoological studies on ultra high dilutions (potencies) were included. Reports were grouped into initial studies, laboratory-internal, multicentre and external replications. Repetition could yield either comparable, or zero, or opposite results. The null-hypothesis was that test and control groups would not be distinguishable (zero effect).
Results: A total of 126 studies were found. From these, 28 were initial studies. When all 98 replicative studies were considered, 70.4% (i.e. 69) reported a result comparable to that of the initial study, 20.4% (20) zero effect and 9.2% (9) an opposite result. Both for the studies until 1994 and the studies 1995-2015 the null-hypothesis (dominance of zero results), should be rejected. Furthermore, the odds of finding a comparable result are generally higher than of finding an opposite result. Although this is true for all three types of replication studies, the fraction of comparable studies diminishes from laboratory-internal (total 82.9%) to multicentre (total 75%) to external (total 48.3%), while the fraction of opposite results was 4.9%, 10.7% and 13.8%. Furthermore, it became obvious that the probability of an external replication producing comparable results is bigger for models that had already been further scrutinized by the initial researchers.
Conclusions: We found 28 experimental models which underwent replication. In total, 24 models were replicated with comparable results, 12 models with zero effect, and 6 models with opposite results. Five models were externally reproduced with comparable results. We encourage further replications of studies in order to learn more about the model systems used.
Homeopathy has been a medical practice recognized worldwide for more than two centuries, performing care, teaching and research activities in several health institutions and medical schools. It employs a clinical approach based on heterodox and complementary scientific principles (principle of therapeutic similitude, homeopathic pathogenetic experimentation, use of individualized medicines and dynamized or potentiated doses), with the aim of awakening a curative response in the body against its own disorders and/or diseases. Based on different premises from those used by conventional medical practice, homeopathy is often the target of unfounded and widespread criticism from individuals who systematically deny homeopathic assumptions and any scientific evidence that proves them due to their pseudoskeptical and pseudoscientific stance, which prevents a correct and bias-free analysis. In order to enlighten doctors, researchers, health professionals and the general public, demystifying culturally rooted dogmatic positions and the pseudoskeptical fallacies that "there is no scientific evidence for homeopathy" and "homeopathy is placebo effect", the Technical Chamber of Homeopathy of the Regional Council of Medicine of the State of São Paulo (TC-Homeopathy, Cremesp) prepared the "Special Dossier Scientific Evidence for Homeopathy" in 2017, made available in three independent editions (online in Portuguese and English; printed in Portuguese) in the Revista de Homeopatia (São Paulo). Then, the dossier was published in Spanish in the La Homeopatía de México journal in 2023 in an edition commemorating the journal's 90th anniversary. Encompassing nine narrative reviews on the various lines of homeopathy research and containing hundreds of scientific articles describing experimental and clinical studies, the Dossier highlighted the state of the art of homeopathic science. Proving and expanding this scientific evidence in 13 chapters, the current work aims to update and clarify knowledge in the area. In addition to elucidating the epistemological premises of the homeopathic model in detail, the work describes the various aspects of basic and clinical research which endorse homeopathic practice and treatment in a continuum of information, data and bibliographic references. The work discusses various topics related to research in homeopathy, covering everything from "homeopathic clinical epidemiology" to "pseudoskeptic and pseudoscientific strategies used in attacks on homeopathy", including "pharmacological basis of the principle of similitude", "experimental studies in biological models", "randomized controlled clinical trials", "systematic reviews, meta-analyses and global reports" and "observational studies", among others. In view of the fact that it becomes fruitless and tiring to describe and analyze all the studies and experiments from the different research lines, we suggest and systematize in the different chapters for those who want to delve deeper into the areas of interest, bibliographical surveys of existing literature through the different databases. As we reiterate throughout the work, despite the difficulties and limitations that exist in developing research in homeopathy due to both methodological aspects and the lack of institutional and financial support, the set of experimental and clinical studies described is indisputable proof that "there is scientific evidence for homeopathy" and "homeopathy is not placebo effect", contrary to falsely disseminated prejudice. However, new studies must continue to be developed to improve clinical practice and elucidate peculiar aspects of the homeopathic paradigm. Acting as an integrative and complementary therapy to other specialties, homeopathy can add efficacy, effectiveness, efficiency and safety to medical practice, acting in a curative and preventive manner, reducing symptomatic manifestations and the predisposition to falling ill, with low cost and minimal adverse events, helping doctors to fulfill their "highest and only mission, which is to make sick people healthy, which is called healing" (Samuel Hahnemann, Organon of Medicine, § 1).
La Homeopatía de México | Evidencias Científicas de la Homeopatía | Edición Especial de Aniversario (90 años) | 2023 || EDITORIAL: Para aquellos que demandan evidencias científicas de la Homeopatía. Marcus Zulian Teixeira. | ARTÍCULOS: Homeopatía: una breve descripción de esta especialidad médica. Marcelo Pustiglione, Eduardo Goldenstein, Y. Moisés Checinski. | Formación médica en la terapéutica no convencional en el mundo (Homeopatía y acupuntura). Marcus Zulian Teixeira. | Bases científicas del principio de curación homeopática en la farmacología moderna. Marcus Zulian Teixeira. | La solidez de la investigación homeopática fundamental. Leoni Villano Bonamin. | Efectos de las diluciones homeopáticas altas sobre los modelos in vitro: revisión de la literatura. Silvia Waisse. | Efectos de las diluciones homeopáticas altas sobre las plantas: revisión de la literatura. Marcus Zulian Teixeira, Solange M.T.P.G. Carneiro. | Investigación clínica en Homeopatía: revisiones sistemáticas y estudios clínicos aleatorizados. Silvia Waisse. | Estrógeno potenciado en el tratamiento homeopático del dolor pélvico asociado a endometriosis: Un estudio aleatorizado, doble ciego, controlado con placebo, de 24 semanas. Marcus Zulian Teixeira, Sérgio Podgaec, Edmund Chada Baracat. | Estudio aleatorizado, doble ciego, sobre la eficacia del tratamiento homeopático en niños con amigdalitis recurrente. Sérgio E. Furuta, Luc L. M. Weckx, Cláudia R. Figueiredo. | ¿Los medicamentos homeopáticos provocan agravación o efectos adversos dependientes de los fármacos? Flávio Dantas. | ¿Los medicamentos homeopáticos inducen síntomas en voluntarios aparentemente sanos? Contribución brasileña al debate sobre los estudios patogénicos homeopáticos. Flávio Dantas. |
La Homeopatía de México | Evidencias Científicas de la Homeopatía | Edición Especial de Aniversario (90 años) | 2023 ||
EDITORIAL:
Para aquellos que demandan evidencias científicas de la Homeopatía.
Marcus Zulian Teixeira. |
ARTÍCULOS:
Homeopatía: una breve descripción de esta especialidad médica.
Marcelo Pustiglione, Eduardo Goldenstein, Y. Moisés Checinski. |
Formación médica en la terapéutica no convencional en el mundo (Homeopatía y acupuntura).
Marcus Zulian Teixeira. |
Bases científicas del principio de curación homeopática en la farmacología moderna.
Marcus Zulian Teixeira. |
La solidez de la investigación homeopática fundamental.
Leoni Villano Bonamin. |
Efectos de las diluciones homeopáticas altas sobre los modelos in vitro: revisión de la literatura.
Silvia Waisse. |
Efectos de las diluciones homeopáticas altas sobre las plantas: revisión de la literatura.
Marcus Zulian Teixeira, Solange M.T.P.G. Carneiro. |
Investigación clínica en Homeopatía: revisiones sistemáticas y estudios clínicos aleatorizados.
Silvia Waisse. |
Estrógeno potenciado en el tratamiento homeopático del dolor pélvico asociado a endometriosis: Un estudio aleatorizado, doble ciego, controlado con placebo, de 24 semanas.
Marcus Zulian Teixeira, Sérgio Podgaec, Edmund Chada Baracat. |
Estudio aleatorizado, doble ciego, sobre la eficacia del tratamiento homeopático en niños con amigdalitis recurrente.
Sérgio E. Furuta, Luc L. M. Weckx, Cláudia R. Figueiredo. |
¿Los medicamentos homeopáticos provocan agravación o efectos adversos dependientes de los fármacos?
Flávio Dantas. |
¿Los medicamentos homeopáticos inducen síntomas en voluntarios aparentemente sanos? Contribución brasileña al debate sobre los estudios patogénicos homeopáticos.
Flávio Dantas. |
Background: This review is part of a special issue of Journal “Homeopathy†(ELSEVIER) to be published in 2015, about the follow-up of researches published in the book titled “Ultra-High Dilution, Physiology and Physicsâ€, written in 1994 and edited by PC Endler and J Schulte. In 2010 a critical and conceptual review about animal models in homeopathy and high dilution research was published by our group. Thus, the aim of this study is to know how models and conclusions have progressed in this field in the last five years. Animal models represent one of the most illustrative examples of the biological effects of homeopathy and high dilutions. The main contribution of these studies is the comprehension of biological features and the phenomenology towards the high dilutions effects upon living systems, which represents an important step to the understanding of mechanisms of action of homeopathic medicines. Methods: 53 articles indexed in the PubMed database were systematically evaluated, in which 12 different animal species were used. 29 out of 53 reported studies were performed with “ultra-high†dilutions, whereas 14 studies were performed using dilutions in the range or below 10-23 or with commercial complexes (10). Results: Only 02 negative results were reported, both using commercial complexes as tested medicine (one each in fish and bee model). Since 2010, the quality of employed methods, mainly statistics, has improved. The inclusion of more refined protocols, such as in vitro primary cell cultures and ex vivo protocols (10/53), often with three or more repetitions, could be observed. These new methods allowed to observe epigenetic mechanisms involved. Conclusion: The demonstration of biological effects of homeopathy on animal models, in the past 5 years, is more refined than those previously described, helping in the development of paths to the mechanism of action discovery.
RIASSUNTO Questo lavoro costituisce una rassegna delle attuali teorie riguardanti la farmaco-dinamica del medicinale omeopatico. E' necessario partire dall'idea che la patolo-gia rappresenti una conseguenza della perturbazione di sistemi molecolari e bio-elettrodinamici nell'organismo: le HD potrebbero trasportare un'informazione in grado di spostare lo squilibrio globale del paziente verso un nuovo "attrattore dinamico" più prossimo allo stato di salute. E' auspicabile un progressivo appro-fondimento in futuro di questi temi. PAROLE CHIAVE Omeopatia, omeodinamica, meccanismo d'azione del rimedio omeopatico, ricerca in omeopatia SUMMARY This work constitutes a review of the present theories regarding the homeody-namics of homeopathic remedies. It is necessary to start from the idea that the pathology represents a consequence of the perturbation of molecular systems in the organism: HD might carry an information able to move the global imbalance of the patient toward a new "dynamic attractor" nearer to the state of health. A progressive widening of these themes is desiderable in future. KEY WORDS Homeopathy, homeodynamic, mechanism of action of homeopathic remedy, homeopathic research.
In July 2017, to demystify the fallacy – or post-truth – asserting “there are no scientific evidence for homeopathy”, the Technical Chamber for Homeopathy, Regional Medical Council of the State of São Paulo (CREMESP, Brazil) published the Special Dossier “Evidências Científicas em Homeopatia”, available online in the scientific journal of the São Paulo Homeopathic Medical Association (APH), Revista de Homeopatia.
After this publication, in view of the request of homeopathic doctors and institutions from other countries, the Technical Chamber for Homeopathy, CREMESP, produced an edition of the dossier in English, “Scientific Evidence for Homeopathy”, which has just been made available online in the Revista de Homeopatia.
Encompassing 9 revisions (and 2 randomized clinical trials) on several lines of homeopathic research, containing hundreds of scientific articles published in various journals, this dossier highlights to the scientific and medical class, as well as to the general public, the state of the art of homeopathic research:
Despite the ongoing difficulties and limitations opposing the development of research in homeopathy – partly due to methodological aspects, and partly to lack of institutional and financial support – the experimental and clinical studies described in this dossier, which ground the homeopathic assumptions and confirm the efficacy and safety of this approach to therapeutics – provide unquestionable proof for the “availability of scientific evidence for homeopathy”, against the false and prejudiced opinion that is widely divulgated.
With the divulgation of the present dossier, prepared with the support of Technical Chamber for Homeopathy, CREMESP, we hope to dispel doubts and sensitize our colleagues as to the validity and relevance of homeopathy as adjuvant treatment complementary to all other medical specialties according to ethical and safe principles. Our overall goals are to broaden the understanding of human disease, increase the therapeutic resources, contribute to the definition and effectiveness of medicine in chronic diseases, minimize the adverse effects of modern drugs and strengthen the patient-doctor relationship, among other aspects. In this way, we will be able to work together, since “The physician’s high and only mission is to restore the sick to health, to cure, as it is termed (Samuel Hahnemann, Organon of medicine, § 1).
Para desmitificar a falácia ou pós-verdade de que “não existem evidências científicas em homeopatia”, disseminada indistintamente em todos os meios, a Câmara Técnica de Homeopatia do Conselho Regional de Medicina do Estado de São Paulo (CREMESP) elaborou o Dossiê Especial “Evidências Científicas em Homeopatia”, que acaba de ser disponibilizado online na Revista de Homeopatia da Associação Paulista de Homeopatia (APH).
Englobando 9 revisões (e 2 RCT) sobre diversas linhas de pesquisa existentes nos mais variados campos da ciência, as quais comportam centenas de artigos científicos publicados em periódicos distintos, esse dossiê evidencia à classe médica e científica, assim como ao público em geral, o estado da arte da pesquisa homeopática.
Apesar das dificuldades e limitações existentes para o desenvolvimento de pesquisas na área, tanto pelos aspectos metodológicos quanto pela ausência de apoio institucional e financeiro, o conjunto de estudos experimentais e clínicos citados, que fundamentam os pressupostos homeopáticos e confirmam a eficácia e a segurança da terapêutica, é prova inconteste de que “existem evidências científicas em homeopatia”, ao contrário do preconceito falsamente disseminado.
Com a elaboração e a divulgação desse dossiê, sob os auspícios da Câmara Técnica de Homeopatia do CREMESP, esperamos esclarecer e sensibilizar os colegas de profissão sobre a validade e a importância do emprego da homeopatia como prática médica adjuvante e complementar às demais especialidades, segundo princípios éticos e seguros, a fim de se ampliar o entendimento do processo de adoecimento humano e o arsenal terapêutico, incrementar o ato médico e sua resolutividade nas doenças crônicas, minimizar os efeitos adversos dos fármacos modernos e fortalecer a relação médico-paciente, dentre outros aspectos. Dessa forma, poderemos trabalhar unidos em torno da “mais elevada e única missão do médico que é tornar saudáveis as pessoas doentes, o que se chama curar” (Samuel Hahnemann, Organon da arte de curar, § 1).
Background:
In the 1990s, a study was performed on the effects of highly diluted thyroxine on frog metamorphosis. This model represented one of the most discussed examples of the biological effects of high dilutions over the next two decades. In 2010, another critical conceptual review of the use of animal models in homeopathy and high-dilution research was published. The main contribution of these studies was the elucidation of the biological features and phenomenology of the effects of high dilutions on living systems, representing an important step forward in our understanding of the mechanisms of action of homeopathic medicines.
Methods:
We performed a further review of this line of investigation using the same methods. Fifty-three articles that were indexed in the PubMed database and used 12 different animal species were systematically evaluated. Only a fraction of the studies (29/53) reported herein were performed with "ultra high" dilutions. The other studies were performed with dilutions in ranges below 10(-23) (14/53 articles) or commercial complexes (10/53 articles).
Results:
Only two articles reported negative results; both used in vivo protocols to test commercial complexes, one in fish and one in bees. The quality of the employed techniques improved in 2010-2014 compared with the studies that were reviewed previously in 2010, with the inclusion of more ethically refined protocols, including in vitro primary cell cultures and ex vivo studies (10/53 articles), often with three or more replicates and analyses of epigenetic mechanisms that were previously unknown in 2010.
Conclusion:
In our updated review of the past 5 years, we found further demonstrations of the biological effects of homeopathy using more refined animal models and in vitro techniques.
The pharmacodynamics aspects of homeopathic remedies are appraised by laboratory studies on the biological effects at various levels (cellular, molecular and systemic). The major question is how these medicines may work in the body. The possible answers concern the identification of biological targets, the means of drug-receptor interactions, the mechanisms of signal transmission and amplification, and the models of inversion of effects according to the traditional 'simile' rule. These problems are handled by two experimental and theoretical lines, according to the doses or dilutions considered (low-medium versus high dilutions). Homeopathic formulations in low-medium dilutions, containing molecules in the range of ultra-low doses, exploit the extreme sensitivity of biological systems to exogenous and endogenous signals. Their effects are interpreted in the framework of hormesis theories and paradoxical pharmacology. The hypotheses regarding the action mechanisms of highly diluted/dynamized solutions (beyond Avogadro-Loschmidt limit) variously invoke sensitivity to bioelectromagnetic information, participation of water chains in signalling, and regulation of bifurcation points of systemic networks. High-dilution pharmacology is emerging as a pioneering subject in the domain of nanomedicine and is providing greater plausibility to the puzzling claims of homeopathy.
This is a systematic review of the animal models used in studies of high dilutions. The objectives are to analyze methodological quality of papers and reported results, and to highlight key conceptual aspects of high dilution to suggest clues concerning putative mechanisms of action.
Papers for inclusion were identified systematically, from the Pubmed-Medline database, using 'Homeopathy' and 'Animal' as keywords. Only original full papers in English published between January 1999 and June 2009 were included, reviews, scientific reports, thesis, older papers, papers extracted from Medline using similar keywords, papers about mixed commercial formulas and books were also considered for discussion only. 31 papers describing 33 experiments were identified for the main analysis and a total of 89 items cited.
Systematic analysis of the selected papers yielded evidence of some important intrinsic features of high dilution studies performed in animal models: a) methodological quality was generally adequate, some aspects could be improved; b) convergence between results and materia medica is seen in some studies, pointing toward to the possibility of systematic study of the Similia principle c) both isopathic and Similia models seem useful to understand some complex biological phenomena, such as parasite-host interactions; d) the effects of high dilutions seem to stimulate restoration of a 'stable state', as seen in several experimental models from both descriptive and mathematical points of view.
Experiments on amphibian metamorphosis can vary considerably in duration. The authors had set themselves the task of defining a generally applicable pooling method for metamorphosis experiments. The problem of artificial differences in variability when comparing and pooling data from several experiments was approached by normalization with respect to time based on the development of both test and the control animals. The range from 0% to 100% over which the fraction of four-legged animals progresses in the course of an experiment is divided into 10%-intervals and the 10% reference points are mapped on a corresponding scale. Each measurement is then assigned to the point on the time scale to which it is closest. In this way each reference point is assigned a value giving the number or percentage of four-legged animals at that point on the scale. Subsequent analysis was then based on the individual values for the test and control groups that corresponded to the joint 10% reference point. Normalization respect to time was done on the assumption that differences in metamorphosis speed attributable to treatment would override differences in duration between experiments. The results of experiments performed over the course of two decades (1990 - 2010) on highland Rana temporaria treated with a homeopathically prepared high dilution of thyroxine ("30x") are presented in full detail based on this normalization method. Differences found between treatment groups thus calculated were in line with those obtained with other pooling methods. Thyroxine 30x does slow down metamorphosis in inert highland amphibians. This was observed by five researchers in 20 sub-experiments, and it seems to be the most reliable bio-assay found in amphibian research on homeopathy so far. When experiments were performed with highland animals pretreated by hyperstimulation with molecular thyroxine, slowing down of metamorphosis was again observed (by three out of four researchers) in most of 10 sub-experiments.
These experiments, performed in Graz and in Utrecht, investigate the influence of extremely dilute thyroxine in a special "homeopathic" preparation on two transitions in the metamorphosis of highland amphibia: a) from the 2-legged to the 4-legged stage; b) from the tailed 4-legged stage to the untailed stage, the juvenile frog (performed in the two laboratories in Graz) or to the stage with reduced tail, respectively (performed in Utrecht).
A homeopathic dilution (T4.30X) of thyroxine in a small but significant range slows down the metamorphosis of highland tadpoles as compared to the reference solution H2O.30X. This effect could be observed for both transitions. The retardation of metamorphosis was independently shown in all 3 laboratories during the course of the metamorphosis season of the highland amphibia (from August to October).
In one experiment (Graz), the number of juvenile frogs climbing out of the water in the final stages of metamorphosis was counted. Fewer "climbers" were observed under treatment with solution T4.30X.
The objective of this study was to develop a criteria catalogue serving as a guideline for authors to improve quality of reporting experiments in basic research in homeopathy. A Delphi Process was initiated including three rounds of adjusting and phrasing plus two consensus conferences. European researchers who published experimental work within the last 5 years were involved. A checklist for authors provide a catalogue with 23 criteria. The "Introduction" should focus on underlying hypotheses, the homeopathic principle investigated and state if experiments are exploratory or confirmatory. "Materials and methods" should comprise information on object of investigation, experimental setup, parameters, intervention and statistical methods. A more detailed description on the homeopathic substances, for example, manufacture, dilution method, starting point of dilution is required. A further result of the Delphi process is to raise scientists' awareness of reporting blinding, allocation, replication, quality control and system performance controls. The part "Results" should provide the exact number of treated units per setting which were included in each analysis and state missing samples and drop outs. Results presented in tables and figures are as important as appropriate measures of effect size, uncertainty and probability. "Discussion" in a report should depict more than a general interpretation of results in the context of current evidence but also limitations and an appraisal of aptitude for the chosen experimental model. Authors of homeopathic basic research publications are encouraged to apply our checklist when preparing their manuscripts. Feedback is encouraged on applicability, strength and limitations of the list to enable future revisions.
In homeopathy, ability of ultra-high diluted drugs at or above potency 12C (diluted beyond Avogadro's limit) in ameliorating/curing various diseases is often questioned, particularly because the mechanism of action is not precisely known. We tested the hypothesis if suitable modulations of signal proteins could be one of the possible pathways of action of a highly diluted homeopathic drug, Secale cornutum 30C (diluted 10(60) times; Sec cor 30). It could successfully combat DMBA + croton oil-induced skin papilloma in mice as evidenced by histological, cytogenetical, immunofluorescence, ELISA and immunoblot findings. Critical analysis of several signal proteins like AhR, PCNA, Akt, Bcl-2, Bcl-xL, NF-κB and IL-6 and of pro-apoptotic proteins like cytochrome c, Bax, Bad, Apaf, caspase-3 and -9 revealed that Sec cor 30 suitably modulated their expression levels along with amelioration of skin papilloma. FACS data also suggested an increase of cell population at S and G2 phases and decrease in sub-G1 and G1 phages in carcinogen-treated drug-unfed mice, but these were found to be near normal in the Sec cor 30-fed mice. There was reduction in genotoxic and DNA damages in bone marrow cells of Sec Cor 30-fed mice, as revealed from cytogenetic and Comet assays. Changes in histological features of skin papilloma were noted. Immunofluorescence studies of AhR and PCNA also suggested reduced expression of these proteins in Sec cor 30-fed mice, thereby showing its anti-cancer potentials against skin papilloma. Furthermore, this study also supports the hypothesis that potentized homeopathic drugs act at gene regulatory level.
We studied the influence of a moderate homeopathically prepared thyroxine dilution (final concentration in the basin water 10-(13) parts by weight) on the metamorphosis of lowland Rana temporaria which had been hyperstimulated with thyroxine. Two groups of animals were pretreated by immersing them in a molecular thyroxine dilution (10-(8) parts by weight). This pretreatment speeds up development, as is well known. In accordance with the homeopathic/isopathic idea of detoxication or cure, the same hormone was then diluted and agitated in successive steps for further treatment. This homeopathically prepared dilution was administered at 24-hour intervals to one of the groups. An analogously prepared blank solution was used for the control group. Our hypothesis, which was derived from earlier studies, was that animals treated with the test solution would metamorphose more slowly than the control animals, i.e. that the homeopathically prepared thyroxine would have a 'curative' effect. In this new series of experiments this hypothesis was examined by 3 independent researchers. In the experiments carried out by 2 of the 3 researchers the number of animals that reached the four-legged stage at defined points in time was smaller in the group treated with homeopathically prepared thyroxine. In the third laboratory no difference was found between the groups. However, the overall inhibiting effect was statistically significant and more pronounced than in earlier, less promising studies and in parallel experiments in which nonprestimulated animals had been used. Other studies carried out by the 3 researchers involved animals from highland biotopes, where the natural environment probably induces a greater sensitivity towards thyroxine or higher thyroxine levels. These animals reacted to the homeopathically prepared thyroxine with a slowing down of metamorphosis, even when they had not been prestimulated with a molecular dose of the hormone. This effect was observed in all 3 laboratories and is consistent with the results of previous studies.
A search of the literature and the experiments carried out by the authors of this review show that there are a number of animal models where the effect of homeopathic dilutions or the principles of homeopathic medicine have been tested. The results relate to the immunostimulation by ultralow doses of antigens, the immunological models of the 'simile', the regulation of acute or chronic inflammatory processes and the use of homeopathic medicines in farming. The models utilized by different research groups are extremely etherogeneous and differ as the test medicines, the dilutions and the outcomes are concerned. Some experimental lines, particularly those utilizing mice models of immunomodulation and anti-inflammatory effects of homeopathic complex formulations, give support to a real effect of homeopathic high dilutions in animals, but often these data are of preliminary nature and have not been independently replicated. The evidence emerging from animal models is supporting the traditional 'simile' rule, according to which ultralow doses of compounds, that in high doses are pathogenic, may have paradoxically a protective or curative effect. Despite a few encouraging observational studies, the effectiveness of the homeopathic prevention or therapy of infections in veterinary medicine is not sufficiently supported by randomized and controlled trials.
The influence of a highly diluted agitated, i.e. homeopathically prepared thyroxin solution (10(-30), final concentration in the basin water 10(-35) parts by weight after the first application) on metamorphosis in lowland Rana temporaria from the spawn stage on was studied. The treatment with homeopathically prepared thyroxin solution (10(-30)) starts at the frogspawn stage. It represents a tool to learn more about the previously standardized amphibian model, where the thyroxin solution was applied from the two-legged stage on only. Lowland frogs were pretreated by immersing spawn in an aqueous molecular thyroxin dilution (10(-8) parts by weight). In later stages of development (2 to 4 legged), this has been found to speed up metamorphosis by around 15%. In accordance with the homeopathic idea of detoxication or cure, hyperstimulated animals (spawn or, in subsequence, larvae) were treated either with thyroxin that had been highly diluted and agitated in successive steps, i.e. homeopathically prepared (10(-30)), or analogously prepared blank solution (water). Development was monitored by documenting the number of animals that had entered the four-legged stage. It has been found that animals treated with the test solution metamorphosed more slowly than the control animals, i.e. the effect of the homeopathically prepared thyroxin was opposed to the usual effect of molecular thyroxin. The number of test animals that reached the 4-legged stage at defined points in time was slightly smaller in the group treated with homeopathically prepared thyroxin at some, but not at all points in time, compared to control. The results in this study sustain the previous multi researcher findings that highly diluted homeopathically prepared thyroxin is able to slow down metamorphosis of Rana temporaria.
The influence of moderately diluted, agitated, i.e., homeopathically prepared, thyroxin solutions (10-11 - 10-21, final concentration in the basin water 0.6 10-15 - 0.6 10-25 parts by weight after the first application) on metamorphosis in highland Rana temporaria from the two-legged stage was studied. In accordance with the homeopathic idea of effects of specially prepared dilutions being inverse to those of their mother substances, animals were treated either with thyroxin 10-11 - 10-21 or analogously prepared blank solution (water). Development was monitored by documenting the number of animals that had entered the four-legged stage. It has been found that animals treated with the thyroxin solutions metamorphosed more slowly than the control animals, i.e., the effect of the homeopathically prepared thyroxin was opposed to the usual effect of molecular thyroxin. The number of test animals that reached the four-legged stage at defined points in time was smaller (2-13.5%) in the group treated with homeopathically prepared thyroxin at the points in time, compared to control. The results in this study sustain the previous multiresearcher findings that show that diluted homeopathically prepared thyroxin is able to slow down metamorphosis of R. temporaria.
Background: Studies performed in 5 laboratories have shown that homeopathically prepared highly diluted thyroxin (10-30 = 30x) slowed down metamorphosis of highland amphibians. Metamorphosis of lowland amphibians, however, could be slowed down by a low dilution of thyroxin (10-8 = 8x) if animals had been artificially pretreated with thyroxin. Objective: To combine the advantages of using animals from highland biotopes and hyperstimulation prior to treatment. Animals and Methods: Rana temporaria from an alpine biotope were pretreated in an aqueous molecular thyroxin dilution (10-8 parts by weight, hyperstimulation). This is supposed to accelerate metamorphosis. In accordance with the homeopathic idea of detoxification or cure, one group of these hyperstimulated animals was then treated with thyroxin 30x, and another group with water 30x. Experiments were performed by 4 independent researchers. Results: As a trend, the thyroxin-30x animals metamorphosed more slowly than the water-30x animals. The number of thyroxin-30x animals that reached the 4-legged stage at defined points in time was slightly smaller at some but not all points in time, compared to control. This is in line with previous findings and can be discussed as an interesting result. Contrary to our working hypothesis, however, differences were not bigger than in the previous experiments in which animals had not been pretreated with thyroxin 10-8. Conclusion: This study supports previous findings but does not prove the assumption that pretreatment of highland animals with molecular thyroxine improves the original protocol.
Ultra High Dilutions (UHD) are diluted beyond the Avogadro limit with dynamization (dilution with succussion). The process of anuran amphibian metamorphosis is controlled by thyroid hormones, including the resorption of the tadpole tail.
A randomized and blinded study was performed to investigate the influence of triiodothyronine (T3) 5·10(-24)M (10cH) on apoptosis induced by T3 100 nM in Rana catesbeiana tadpoles' tail tips, in vitro. Explants were randomized to three groups: control: no T3 in pharmacological or UHD dose; test: T3 100 nM and challenged with T3 10cH (UHD); positive control: T3 100 nM, treated with unsuccussed ethanol. The apoptotic index and the area of explants of test and control groups at the first and final day of the experiment were compared by t-test.
There was no difference in tail tip area between test and control groups, but a significantly higher (p<0.01) index of apoptosis in explants of the test group.
This data suggest that T3 10cH modifies the effect of T3 at pharmacological dose, opening new perspectives for further studies and investigation of the dose-effect curve.
To the Editor: Reproducibility is the cornerstone of any scientific method. We have recently shown in the pages of this journal that standardization in mouse experiments—that is, standardization in the characteristics of the animals used (such as age, sex, body weight and others), husbandry and test procedures—may generate spurious results, accounting for poor reproducibility.
We studied the influence of specially prepared highly diluted thyroxine on the spontaneous tendency of juvenile frogs, which were at the end of thyroxine-controlled metamorphosis, to leave the water and climb onto land. The test dilution with a thyroxine concentration beyond Avogadro's value (dilution thyroxine D30) and the reference (dilution water D30) were prepared according to directions from the literature on homeopathy. A few drops of these solutions were added to tap water of basins containing the frogs. The frogs' climbing activities were monitored immediately after adding the solutions. The hypothesis derived from a preliminary study was that there is less climbing activity in frogs treated with dilution thyroxine D30 than in a reference group. This hypothesis was proven. Climbing activity diminished under the influence of dilution thyroxine D30, with statistical significance both in comparison to the effect of the analogously prepared solvent (dilution water D30) as well as in comparison to control observations before the start of treatment. When in a later step of observation the dilution water D30-control group was treated with dilution thyroxine D30, the diminishing effect on activity also occurred.
One strand of research on the scientific basis of homeopathy is based on inversion effects of dilutions and the biophysical properties of information transfer. A model developed by Endler, was the basis for the study of the influence of high-diluted solution (1:1026 part by weight) of thyroid glands on the rate of metamorphosis of the frog Rana catesbeiana from the no legged to four-legged stage. The glands were obtained from tadpoles and prepared according by (dilution and succussion). Similar pure hydroalcoholic solution (unsuccussed) was used as control. In order to identify significant differences in the frequencies of four-legged tadpoles, in homeopathic and control group, we used a chi-square goodness-of-fit test (P<0.01) and the cumulative risk for metamorphosis by Cox's Proportional Hazards model (P<0.05). The number of animals that reached the four-legged stage is generally smaller in the treated group, than in the hydroalcoholic control group. It was postulated that thyroid hormones transmitted information' specific to the molecules used to prepare the solution, even though the molarity was beyond Avogadro's number.
Studies performed in 5 laboratories have shown that homeopathically prepared highly diluted thyroxin (10(-30)=30x) slowed down metamorphosis of highland amphibians. Metamorphosis of lowland amphibians, however, could be slowed down by a low dilution of thyroxin (10(-8)=8x) if animals had been artificially pretreated with thyroxin.
To combine the advantages of using animals from highland biotopes and hyperstimulation prior to treatment.
Rana temporaria from an alpine biotope were pretreated in an aqueous molecular thyroxin dilution (10(-8) parts by weight, hyperstimulation). This is supposed to accelerate metamorphosis. In accordance with the homeopathic idea of detoxification or cure, one group of these hyperstimulated animals was then treated with thyroxin 30x, and another group with water 30x. Experiments were performed by 4 independent researchers.
As a trend, the thyroxin-30x animals metamorphosed more slowly than the water-30x animals. The number of thyroxin-30x animals that reached the 4-legged stage at defined points in time was slightly smaller at some but not all points in time, compared to control. This is in line with previous findings and can be discussed as an interesting result. Contrary to our working hypothesis, however, differences were not bigger than in the previous experiments in which animals had not been pretreated with thyroxin 10(-8).
This study supports previous findings but does not prove the assumption that pretreatment of highland animals with molecular thyroxine improves the original protocol.
A simplified table for staging anuran embryos and lar-vae with notes on identification Homeopathically prepared dilution of Rana cates-beiana thyroid glands modifies its rate of metamorphosis
- Kl Gosner
- Ferreira Cm
- Guimaraes Hmb
- Saldiva Phn
- Capelozzi
- Vl
Gosner KL. A simplified table for staging anuran embryos and lar-vae with notes on identification. Herpetologica 1960; 16: 183e190. 25 Guedes JRP, Ferreira CM, Guimaraes HMB, Saldiva PHN, Capelozzi VL. Homeopathically prepared dilution of Rana cates-beiana thyroid glands modifies its rate of metamorphosis. Homeop-athy 2004; 93: 132e137.
The metamorphosis of amphibians and information of thyroxine
- Endler
Influence of homeopathically and not homeopathically prepared thyroxine solutions on metamorphosis speed in the grass frog
- C Heckmann
Treatment of frogs with homeopathically prepared thyroxine (10e-10, 10e-20)
- Lingg
On the effect of extremely diluted (“homeopathic”) solutions of metal salts on development and growth of tadpoles
- Koenig
Examination of a hypothesis on the indirect influence of potentized thyroxine solutions on metamorphosis speed in Rana temporaria. Doctoral thesis
- D Dieterle
Special influence of potentized thyroxine solutions on metamorphosis speed in Rana temporaria
- J A Alex
Homeopathy research – an expedition report. An old healing system gains plausibility
- Endler