Scientific guidelines for preclinical research on potentised preparations manufactured according to current pharmacopoeias-the PrePoP guidelines.

OBJECTIVE: Pharmacopoeias regulate the manufacture of potentised pharmaceutical preparations used in different branches of complementary and integrative medicine. The physicochemical properties and biological activity of these preparations are often investigated in preclinical research, yet no guidelines for experimental research currently exist in this area. The present PrePoP guidelines aim to provide recommendations to promote high-quality, statistically sound, and reproducible preclinical research on potentised preparations. METHODS: Input was gathered from researchers nominated by the relevant scientific societies using a simplified Delphi consensus approach covering the most relevant aspects of basic research methodology in the field including appropriate controls, sample preparation and handling, and statistics. After three rounds of feedback, a consensus was finally reached on the most important aspects and considerations for conducting high-quality research on potentised preparations. RESULTS: We present a series of recommendations on a range of topics including experimental controls, system stability, blinding and randomisation, environmental influences, and procedures for the preparation of potentised samples and controls, and we address some specific challenges of this research field. CONCLUSION: This expert consensus process resulted in a robust set of methodological guidelines for research on potentised preparations and provides a valuable framework that will inform and improve the quality of subsequent research in this emerging field. PLEASE CITE THIS ARTICLE AS: Tournier AL, Bonamin LV, Buchheim-Schmidt S, Cartwright S, Dombrowsky C, Doesburg P, Holandino C, Kokornaczyk MO, van de Kraats EB, López-Carvallo JA, Nandy P, Mazón-Suástegui JM, Mirzajani F, Poitevin B, Scherr C, Thieves K, Würtenberger S, Baumgartner S. Scientific guidelines for preclinical research on potentised preparations manufactured according to current pharmacopoeias-the PrePoP guidelines. J Integr Med. 2024; Epub ahead of print.

La "Memoria del Agua" y su Origen Homeopático / The "Memory of Water" and Your Homeopathic Origin

A tres décadas de la publicación del artículo científico que divulgó internacionalmente las investigaciones dirigidas por el doctor Jacques Benveniste en torno a la degranulación de basófilos disparada por anticuerpos altamente diluidos (fenómeno conocido de manera coloquial como "la memoria del agua"), el doctor Bernard Poitevin, quien fue colaborador en dichos estudios científicos, expone en este artículo su versión de la historia y sus puntos de vista sobre este episodio de especial trascendencia para la Homeopatía. En ese sentido, el presente documento nos contextualiza en el panorama que se vivía en torno a la medicina hahnemanniana en Francia desde finales de la década de 1970 y nos muestra ciertos detalles poco recordados sobre el trabajo de Benveniste: cómo se definió la metodología de la investigación, la forma en que se constituyó el equipo de trabajo y el papel que desempeñaron la industria farmacéutica homeopática, el sistema de salud francés y un lobby o grupo de presión contrario a la Homeopatía. Más aún, el artículo nos presenta al doctor Benveniste sin idealizaciones y nos sugiere que ciertos rasgos de su personalidad pudieron influir en el desarrollo de sus investigaciones y en la presentación de los resultados ante la comunidad científica, lo que a su vez pudo repercutir en las discusiones mediáticas que sucedieron en los siguientes años y cuyas consecuencias persisten hasta nuestros días. (AU)

Three decades after the publication of the scientific article on the research conducted by Dr. Jacques Benveniste on the degranulation of basophils triggered by highly diluted antibodies (a phenomenon known colloquially as "the memory of water"), Dr. Bernard Poitevin, who collaborated in the realization of such scientific studies, exposes in this article his version of history and his views on this episode of special significance for the Homeopathy. In this sense, the present document contextualizes us in the panorama that was lived around the Hahnemannian medicine in France since the end of the 1970s and shows us certain little-remembered details about the work directed by Benveniste: how the research methodology was defined, the way the research group was constituted and the role played by the homeopathic pharmaceutical industry, the health system of France and a lobby against Homeopathy. Moreover, the article presents a Dr. Benveniste without idealizations and suggests that certain features of his personality could influence the development of his research and the presentation of results to the scientific community, which in turn could affect the media discussions that happened in the following years and whose consequences persist to this day. (AU)

Pru p 7 sensitization is a predominant cause of severe, cypress pollen-associated peach allergy.

BACKGROUND: Peach is a common elicitor of food allergic reactions. Peach-induced immediate reactions may occur as benign pollen-food syndromes, usually due to birch pollen-related PR-10 cross-reactivity in temperate climates, and as potentially severe primary food allergies, predominantly related to nsLTP Pru p 3 in Mediterranean regions. The newly described peach allergen Pru p 7 has gained recent attention as a potential peach allergy severity marker. Sensitization to Pru p 7 and its allergenic homologues of the gibberellin-regulated protein family occurs in areas with high Cupressaceae tree pollen exposure. OBJECTIVE: We sought to investigate the distribution, clinical characteristics and molecular associations of Pru p 7 sensitization among subjects with suspected peach allergy in different regions of France. METHODS: Subjects with suspected peach allergy (n = 316) were included. Diagnostic work-up was performed according to current guidelines, including open food challenge when required. IgE antibody measurements and competition experiments were performed using the ImmunoCAP assay platform. RESULTS: Sensitization to Pru p 7 was present in 171 (54%) of all subjects in the study and in 123 of 198 (62%) diagnosed as peach allergic, more than half of whom were sensitized to no other peach allergen. Frequency and magnitude of Pru p 7 sensitization were associated with the presence of peach allergy, the clinical severity of peach-induced allergic reactions and the level of cypress pollen exposure. Cypress pollen extract completely outcompeted IgE binding to Pru p 7. Pru p 7 was extremely potent in basophil activation tests. CONCLUSION AND CLINICAL RELEVANCE: A subtype of Cupressaceae pollinosis, characterized by Pru p 7 sensitization, can be an underlying cause of severe peach allergy.

Survey of immuno-allergological ultra high dilution research.

BACKGROUND: Experiments about basic research in Immuno-allergology reported by M. Bastide and B. Poitevin in Ultra High Dilution (1994) have been appraised from a 20 year perspective. The numerous experiments published mainly focus on immunological regulation, inflammatory process and basophil activation. They are analyzed according to one essential criterion: repeatability. METHODS: The commentary reflects the research details made available in a recently published literature review, also published in French. RESULTS: The regulatory effect of high dilution of bursin on immune response has been observed in multiple experiments but not reproduced by independent teams. The immunomodulating effect of Thymulin has been confirmed in mice. Rhus toxicodendron has an anti-inflammatory activity on different models, from mother tincture (TM) to very high dilutions. The homeopathic complex Canova activates macrophages in vitro and in vivo, induces lymphocyte proliferation, and reduces the size of tumors and mortality of sarcoma-bearing mice. Some homeopathic medicines used in clinical inflammation modulate in vitro the neutrophil activation, with variability in the protocols used and in the medicines tested. In allergology, high dilution histamine has an inhibitory effect on basophil activation in multicenter trials and with independent teams, either with methods implying a change in basophil staining or with flow cytometry. However, high dilution histamine had no effect in some well-conducted experiments. The inhibitory effect of Apis mellifica has not been studied with the flow cytometry method, as well as the activation of basophil by anti-IgE high dilution, published in Nature. CONCLUSIONS: Despite considerable research activity in immuno-allergology and a great increase in the number of publications, there is still not in this domain a "gold standard" trial in basic research in homeopathy. The most studied system, the inhibitory effect of histamine high dilutions on basophil activation, requires clarifications of various factors, including individual sensitivity. For scientific and epistemological reasons, the same work should be carried out for independent reproduction of the experiments conducted with anti-IgE and Apis mel high dilution, in complement of the new axes of research in immunoallergology developed since 20 years.

Las grandes directrices de la investigación en homeopatía (parte 2 de 2) / he broad guidelines of research in homeopathy (part 2 of 2)

La primera parte de este artículo se dedicó a presentar las líneas de investigación biológica experimental que se realizan en la Homeopatía; ahora, esta segunda entrega se enfoca, de inicio, en la presentación y el análisis de 25 estudios de notable calidad metodológica que permiten evaluar científicamente la eficacia clínica de la medicina hahnemanniana. Cabe decir que a pesar de que la realización de estos trabajos es complicada y de que sus resultados varían, en conjunto nos ayudan a concluir que “no es tan fácil afirmar, como una simple visión general, que la Homeopatía es un placebo”. A continuación, el doctor Bernard Poitevin enlista las hipótesis que distintos grupos de científicos han tratado de corroborar o desmentir para dar respuesta a una de las interrogantes más frecuentes que se le plantean a la Homeopatía: cuál es el mecanismo de acción del medicamento homeopático (y, en consecuencia, qué tipo de información tiene y de qué manera interactúa con el organismo del paciente). Los resultados obtenidos hasta ahora no son concluyentes, ya que este tipo de investigaciones son todavía muy recientes. Finalmente, el autor nos recuerda que la Homeopatía es una disciplina evolutiva y, como tal, debe eludir los dogmatismos e incluso cuestionar sus principios fundamentales cuando sea necesario. Sólo a través de la investigación a fondo de aquellos problemas científicos que plantea la Homeopatía será posible acallar las críticas y, sobre todo, se tendrá un mejor conocimiento de esta disciplina médica, lo que en consecuencia mejorará su aplicación y efectividad...

The first part of this paper was dedicated to show the lines of experimental biological research being conducted in homeopathy; now, this second part focuses, at first, to the presentation and analysis of 25 studies of high methodological quality that allows to evaluate scientifically the clinical efficacy of Hahnemann’s medicine. We can say that although the realization of these studies is complicated and that their results may vary, together they help us to conclude that “it is not so easy to say, as a simple overview that homeopathy is a placebo”. Then Dr. Bernard Poitevin lists the hypothesis that different groups of scientists have tried to corroborate or deny to answer one of the most frequent questions posed to homeopathy: what is the mechanism of action of homeopathic medicine (and therefore what type of information does it has and how it interacts with the patient’s body). The results so far are inconclusive, since this type of research is still very recent. Finally, the author reminds us that homeopathy is an evolving discipline and, as such, must avoid dogmatism and even to question its fundamental principles when necessary. Only through a profound research of those scientific problems that Homeopathy propose It will be possible to silence criticism and, above all, we will have a better knowledge of this medical discipline, which consequently will improve its implementation and effectiveness...

Las grandes directrices de la investigación en homeopatía (parte 2 de 2) / he broad guidelines of research in homeopathy (part 2 of 2)

La primera parte de este artículo se dedicó a presentar las líneas de investigación biológica experimental que se realizan en la Homeopatía; ahora, esta segunda entrega se enfoca, de inicio, en la presentación y el análisis de 25 estudios de notable calidad metodológica que permiten evaluar científicamente la eficacia clínica de la medicina hahnemanniana. Cabe decir que a pesar de que la realización de estos trabajos es complicada y de que sus resultados varían, en conjunto nos ayudan a concluir que “no es tan fácil afirmar, como una simple visión general, que la Homeopatía es un placebo”. A continuación, el doctor Bernard Poitevin enlista las hipótesis que distintos grupos de científicos han tratado de corroborar o desmentir para dar respuesta a una de las interrogantes más frecuentes que se le plantean a la Homeopatía: cuál es el mecanismo de acción del medicamento homeopático (y, en consecuencia, qué tipo de información tiene y de qué manera interactúa con el organismo del paciente). Los resultados obtenidos hasta ahora no son concluyentes, ya que este tipo de investigaciones son todavía muy recientes. Finalmente, el autor nos recuerda que la Homeopatía es una disciplina evolutiva y, como tal, debe eludir los dogmatismos e incluso cuestionar sus principios fundamentales cuando sea necesario. Sólo a través de la investigación a fondo de aquellos problemas científicos que plantea la Homeopatía será posible acallar las críticas y, sobre todo, se tendrá un mejor conocimiento de esta disciplina médica, lo que en consecuencia mejorará su aplicación y efectividad. (AU)

The first part of this paper was dedicated to show the lines of experimental biological research being conducted in homeopathy; now, this second part focuses, at first, to the presentation and analysis of 25 studies of high methodological quality that allows to evaluate scientifically the clinical efficacy of Hahnemann’s medicine. We can say that although the realization of these studies is complicated and that their results may vary, together they help us to conclude that “it is not so easy to say, as a simple overview that homeopathy is a placebo”. Then Dr. Bernard Poitevin lists the hypothesis that different groups of scientists have tried to corroborate or deny to answer one of the most frequent questions posed to homeopathy: what is the mechanism of action of homeopathic medicine (and therefore what type of information does it has and how it interacts with the patient’s body). The results so far are inconclusive, since this type of research is still very recent. Finally, the author reminds us that homeopathy is an evolving discipline and, as such, must avoid dogmatism and even to question its fundamental principles when necessary. Only through a profound research of those scientific problems that Homeopathy propose It will be possible to silence criticism and, above all, we will have a better knowledge of this medical discipline, which consequently will improve its implementation and effectiveness. (AU)

Las grandes directrices de la investigación en homeopatía (parte 1 de 2) / The broad guidelines of research in homeopathy (part 1 of 2)

La Homeopatía se fundó sobre un método que es, al mismo tiempo, experimental y empírico. La Homeopatía es parcialmente experimental debido a que su semiología nació con la experimentación sobre el hombre sano, efectuada según el método hahnemanniano; asimismo, es parcialmente empírica porque se basa en el trabajo de observación de los médicos homeópatas y en la adquisición de la experiencia práctica, la cual ha sido transmitida a alumnos deseosos de utilizar este método terapéutico. La investigación en Homeopatía se ha desarrollado progresivamente, tratando de integrar las aportaciones de estos dos métodos: experimental y empírico. De hecho, los esfuerzos realizados por situar a la Homeopatía dentro de una metodología rigurosa se remontan al inicio mismo de esta disciplina, inscrita desde su origen por Hahnemann dentro de la línea científica y médica original...

Homeopathy is in part experimental because the semiology was born with the experimentation on the healthy man, which was performed according to Hahnemann´s method; it is also partly empirical because much work is based on the observation of homeopaths and the acquisition of practical experience, which has been transmitted to students eager to use this therapeutic method. Research in Homeopathy has been gradually developed, trying to integrate the contributions of these two methods: experimental and empirical. In fact, efforts have been made to place homeopathy within a rigorous methodology dating back to the beginning of the discipline itself, from its origin registered by Hahnemann within the original scientific and medical field...

Las grandes directrices de la investigación en homeopatía (parte 1 de 2) / The broad guidelines of research in homeopathy (part 1 of 2)

La Homeopatía se fundó sobre un método que es, al mismo tiempo, experimental y empírico. La Homeopatía es parcialmente experimental debido a que su semiología nació con la experimentación sobre el hombre sano, efectuada según el método hahnemanniano; asimismo, es parcialmente empírica porque se basa en el trabajo de observación de los médicos homeópatas y en la adquisición de la experiencia práctica, la cual ha sido transmitida a alumnos deseosos de utilizar este método terapéutico. La investigación en Homeopatía se ha desarrollado progresivamente, tratando de integrar las aportaciones de estos dos métodos: experimental y empírico. De hecho, los esfuerzos realizados por situar a la Homeopatía dentro de una metodología rigurosa se remontan al inicio mismo de esta disciplina, inscrita desde su origen por Hahnemann dentro de la línea científica y médica original. (AU)

Homeopathy is in part experimental because the semiology was born with the experimentation on the healthy man, which was performed according to Hahnemann´s method; it is also partly empirical because much work is based on the observation of homeopaths and the acquisition of practical experience, which has been transmitted to students eager to use this therapeutic method. Research in Homeopathy has been gradually developed, trying to integrate the contributions of these two methods: experimental and empirical. In fact, efforts have been made to place homeopathy within a rigorous methodology dating back to the beginning of the discipline itself, from its origin registered by Hahnemann within the original scientific and medical field. (AU)

Las bases científicas de la homeopatía / The scientific basis of homeopathy

A través de un recorrido por los principios de la Homeopatía y la evolución de sus ideas es posible delimitar las líneas de investigación que podrían desarrollarse para responder las dudas e interrogantes que surgen de la aplicación de esta disciplina,situada entre las ciencias médicas, humanas, biológicas y físicas.A continuación se presenta el resumen de diversas investigaciones que han comprobado, por ejemplo, que los medicamentos homeopáticos sí actúan en células, modelos animales y seres humanos, aunque no se ha logrado explicarcómo; además, se pone de manifiesto que los criterios para evaluar no pueden ser idénticos a los que se emplean en la farmacología clásica, si bien existe cierta similitud.Se concluye que a pesar de que hay demasiados aspectos de la Homeopatía que siguen sin tener una explicación coherente en términos científicos clásicos, no deben rechazarse sin miramientos, sino estudiarse.

Through a tour of the principles of homeopathy and the evolution of his ideas is possible to delineate the lines of research that could be developed to answer the doubts and questions that arise from the application of this discipline, between the medical and social sciences, biological and physical.The summary of several studies that have found, for example is presented, that homeopathic medicines do act on cells, animal models and humans, but has not been able to explainhow; moreover, shows that the criteria for evaluating may not be identical to those used in classical pharmacology, while there is some similarity.We conclude that although there are too many aspects of homeopathy that still lack a coherent explanation in classical scientific terms, should not be rejected without consideration, but studied.

Las bases científicas de la homeopatía / The scientific basis of homeopathy

A través de un recorrido por los principios de la Homeopatía y la evolución de sus ideas es posible delimitar las líneas de investigación que podrían desarrollarse para responder las dudas e interrogantes que surgen de la aplicación de esta disciplina,situada entre las ciencias médicas, humanas, biológicas y físicas.A continuación se presenta el resumen de diversas investigaciones que han comprobado, por ejemplo, que los medicamentos homeopáticos sí actúan en células, modelos animales y seres humanos, aunque no se ha logrado explicarcómo; además, se pone de manifiesto que los criterios para evaluar no pueden ser idénticos a los que se emplean en la farmacología clásica, si bien existe cierta similitud.Se concluye que a pesar de que hay demasiados aspectos de la Homeopatía que siguen sin tener una explicación coherente en términos científicos clásicos, no deben rechazarse sin miramientos, sino estudiarse. (AU)

Through a tour of the principles of homeopathy and the evolution of his ideas is possible to delineate the lines of research that could be developed to answer the doubts and questions that arise from the application of this discipline, between the medical and social sciences, biological and physical.The summary of several studies that have found, for example is presented, that homeopathic medicines do act on cells, animal models and humans, but has not been able to explainhow; moreover, shows that the criteria for evaluating may not be identical to those used in classical pharmacology, while there is some similarity.We conclude that although there are too many aspects of homeopathy that still lack a coherent explanation in classical scientific terms, should not be rejected without consideration, but studied. (AU)