Considera

Plant-based bioassays

Plant-based bioassays have been applied in basic research in homeopathy for a long time. Recent systematic reviews identified 192 publications describing 202 experimental studies that were assessed in terms of reporting quality. Within the set of studies with sufficient reporting quality, 42 experimental studies used statistical methods as well as adequate controls to identify specific effects of homeopathic preparations against placebo. Forty out of these 42 studies (95%) yielded empirical evidence for specific effects, with 18 studies ensuring experimental system stability by systematic negative control experiments. Based on the given set of experimental investigations we conclude that the placebo hypothesis must be dismissed. The study results obtained call for further investigations to identify the mode of action of homeopathic preparations.

Plant-based bioassays have a long tradition in homeopathic basic research. This research approach relies on organisms that are more complex and differentiated than single cells, but do not raise any ethical concerns (as in animal or clinical research). Plant-based bioassays can be grouped into four main areas: assays with unimpaired plants, assays with abiotically stressed plants, phytopathological models, and agricultural field trials.

The research field of plant-based bioassays has been reviewed systematically in 2009/2011 (Betti et al., Majewski et al., Jäger et al.), and a thorough update was published by Ücker et al. in 2018. In this review, a manuscript information score (MIS) was used to assess the reporting quality of the papers. Further quality criteria included the use of statistical models to assess the results, and the use of adequate controls to reliably identify specific effects of homeopathic preparations.

In total, 192 publications were found describing 202 experimental studies. 119 studies included inferential or descriptive statistics, and 74 were rated with MIS > 5 (out of 10 points), thus allowing proper and detailed interpretation. Forty-two out of these 74 studies used succussed or potentized controls to identify specific effects of homeopathic preparations. Forty out of 42 studies (95%) reported significant effects against controls, including dilution levels beyond the inverse Avogadro’s number. Many single studies with diverse methods, and only a few replication trials were identified. 18 studies reported on the use of systematic negative control (SNC) experiments to assess the stability of the experimental set-up.

The quality of the studies increased in recent years. In the update by Ücker et al., covering the time period of 2009/2011-2017, all studies (100%) used some kind of statistical analysis, compared to 50% of the studies from the period 1920-2008/2010. The percentage of publications reaching at least 5 points in the MIS increased from about 60% (1920–2008/2010) to about 75% (2009/2011–2017), and the percentage of studies conducting systematic negative control experiments nearly doubled to 23% compared to the first reviews of 2009/2011.

The most consistent and intriguing result of these reviews is the observation of alternating biologically effective and ineffective potency levels within a series of potency levels of a given substance. All studies that tested series of consecutive potency levels reported such a non-linear and discontinuous relationship between effect and potency level. The specific form of this dose-response-relationship was different for each combination of experimental bioassay and substance potentized. The corresponding “pattern” of effective and ineffective potency levels within a given experimental system proved to be reproducible over weeks to months but seemed to be subject to change after a longer period of time (years). Since such non-linear effects may be considered as surprising and unexpected, they highlight the need for highly controlled experimental set-ups to exclude false-positive results. The best way to control and document the stability of the experimental set-up are SNC experiments, which were implemented in 18 out of 42 studies in these reviews, and yielded evidence for stable experimental conditions.

It is remarkable that 40 out of the 42 studies which used succussed or potentized controls, reported significant effects against controls. One may suspect a publication bias, e.g. the withholding of trials without significant effects. Due to the heterogeneity of the experimental designs and outcomes, a quantitative meta-analysis could not be performed; correspondingly, there is no available estimation of the number of possibly unpublished trials to achieve a zero result in meta-analysis. Based on our experience in the field, we assume it highly unlikely that there should exist a sufficient and larger number of unpublished studies reporting non-significant effects to outweigh 40 published studies reporting significant effects.

Summarizing, in 95% of all published investigations of homeopathic preparations with whole-plant bioassays, significant effects of homeopathic preparations were observed against adequate controls. We thus conclude that there is strong evidence for specific effects of homeopathic preparations over placebo. The empirical observation base thus justifies and calls for further investigations to identify the mode of action of homeopathic preparations.

Homeopathy is not Placebo Effect
Proof ofthe scientific evidence for homeopathy

Marcus Zulian Teixeira (Autor, Editor)

Homeopathy was founded in 1796 by the German physician Samuel Hahnemann. It is an integrative medical practice that uses a clinical approach based on four heterodox and complementary scientific assumptions (principle of therapeutic similarity, homeopathic pathogenetic experimentation, use of individualized medicines and in dynamized doses), with the aim to awaken a healing response from the body against its own disorders.

In addition to these scientific premises, the homeopathic epistemological model also uses vitalist and miasmatic philosophical conceptions to expand understanding of the complex process of human illness, attributing to the imbalance of the organic vital force and the manifestation of chronic miasms the primary and fundamental causes of the diseases, respectively. Supported by conceptual, functional and experimental correlations, this homeopathic vital force would find its representation or biological substrate in the genome (exome plus epigenome), while the chronic miasms would be biologically represented by the disease-promoting epigenetic alterations.

Because it is based on epistemological premises that are different from conventional medical practice, homeopathy is generally poorly understood, suffering criticism from prejudiced individuals who systematically deny homeopathic principles and any scientific evidence that proves them. In reality, they are pseudoskeptics masquerading as pseudoscientists.

In order to enlighten everyone and demystify culturally ingrained pseudoskeptical fallacies (such as, “there is no scientific evidence for homeopathy” and “homeopathy is placebo effect”), the Technical Chamber for Homeopathy of the Regional Medical Council of the State of Sao Paulo (Cremesp) produced the Special Dossier “Scientific Evidence for Homeopathy” in 2017, available in open access trilingual editions (Por-tuguese, English and Spanish) in the Revista de Homeopatia (Sao Paulo)and La Homeopatía de Mexico scientific journals.

This Dossier is composed of nine narrative research reviews in several medical science fields (historical, social, medical education, pharmacological, basic, clinical, patient safety and pathogenetic experimentation), encompassing hundreds of scientific articles describing experimental and clinical studies. It seeks to highlight the state of the art of homeopathic research.

Then, in order to expand and update this scientific evidence for homeopathy, the authors published the electronic book (e-book, PDF editing) in Portuguese “Homeopatia nao e efeito placebo: comprova ̧cao dasevidencias científicas da homeopatia” in 2023, which was translated into English and Spanish in 2024 (“Homeopathy is not placebo effect”: proof of scientific evidence for homeopathy / “La homeopatía no es efecto placebo”:comprobacion de las evidencias científicas en homeopatía), being made available in open access editions in the Virtual Health Library (VHL-LILACS-BIREME)11-13 and in the USP Open Books Portal,14,15 increasing knowledge of the area in 13 interactive chapters.

In turn, this trilingual book series were also made available in EPUB editing (Kindle, Amazon) to expand the dissemination scope of the material, and we are inviting homeopaths from other countries to collaborate in translating it into other languages.

Starting the work, the chapter “Homeopathy” discusses the epistemological premises of the homeopathic model (principle of therapeutic similitude, homeopathic pathogenetic experimentation, use of individualized medicines and in dynamized doses)1 in detail, describing its evidence in general and providing the reader with an overview of treatment and clinical practice in homeopathy.

Then in the chapter “Clinical epidemiology in homeopathy”, the principles of homeopathic clinical epidemiology are addressed after a review of the principles of classical clinical epidemiology and the types of epidemiological studies used to evaluate the efficacy and effectiveness of conventional treatments, as well as the types of epidemiological studies in homeopathy. It is worth highlighting that the epistemological premise of “individualization of homeopathic treatment in view of the symptomatic totality characteristic of the patient-disease binomial” is a sine qua non condition for dynamized homeopathic medicine (ultra-diluted and with infinitesimal pathogenetic power) to be able to awaken a curative response.

Next, in addition to general databases (LILACS and PubMed), several specific homeopathic databases are described in the chapter “Overview of homeopathy research − Databases”; these databases group together a wide range of homeopathic studies indexed in the areas of basic and clinical research, from experimental studies in biological and physico-chemical models (Homeopathy Basic Research Experiments database, HomVet CRdatabase and PROVINGS.INFO database) through to epidemiological clinical studies of all types (Clinical Outcome Research in Homeopathy, Homeopathic Intervention Studies and CAM-QUEST databases).

The principle of similitude (similarity) is approached according to the homeopathic model and modern pharmacology in the chapter “Pharmacological basis of the principle of similitude”, describing hundreds of experimental and clinical studies that support the curative response of homeopathic treatment (vital reaction or therapeutic similarity) in accordance with manifestations of the rebound effect of modern drugs (paradoxical reaction of the organism). Furthermore, it describes the proposal to use modern drugs according to the principle of therapeutic similitude, using the rebound effect of drugs curatively.

In the field of basic research in homeopathy, the chapter “Experimental studies in biological models (in vitro, plants and animals)” describes hundreds of experimental studies in cells, plants and animals that demonstrate the superiority of homeopathic medicine over control groups, highlighting that “homeopathy is not placebo effect” in systematic reviews and meta-analyses.

In the field of clinical research in homeopathy, the chapter “Randomized Controlled Clinical Trials (RCTs)” describes dozens of randomized, double-blind and placebo-controlled clinical trials (level of evidence 1B) of good methodological quality which demonstrate the effectiveness of the homeopathic treatment versus placebo. Four chapters address systematic reviews of RCTs, global (any clinical indication)and specific (specific clinical indication) with and without meta-analyses, increasing the level of evidence (1A) of the clinical effectiveness of homeopathy.

In the chapter “Systematic reviews and global reports with positive results of homeopathy compared to placebo”, five global systematic reviews of RCTs with meta-analyses are described which demonstrate the superiority of homeopathic treatment over placebo. On the other hand, two global systematic reviews of RCTs, one with meta-analysis and the other without, are described in the chapter “Systematic reviews and global reports with negative results of homeopathy com-pared to placebo (Methodological flaws)”. These presented negative results of homeopathy compared to placebo, however numerous biases and methodological flaws in the studies are evidenced, as demonstrated in several post-hoc analyses published later.

Confirming these post-hoc analyses, a systematic review of global systematic reviews of RCTs with meta-analyses described previously was published in 2023, demonstrating that “global systematic reviews of homeopathic RCTs with meta-analyses reveal significant positive effects of homeopathy compared to placebo”, and that “there was no support for the alternative hypothesis of no outcome difference between homeopathy and placebo”.

Specific systematic reviews are described in the chapter “Systematic reviews for specific clinical conditions”, which demonstrated the superiority of homeopathy over placebo in several clinical conditions: with metaanalyses (allergic rhinitis, acute childhood diarrhea, postoperative ileus and attention deficit disorder with hyperactivity) and without meta-analyses (acute otitis media, postoperative inflammation, psychiatric disorders and rheumatic diseases).

Then in the chapter “Observational studies”, analytical observational studies (level of evidence 2B) were mainly addressed, describing robust cohort studies that presented important information about the effective-ness and cost-effectiveness of homeopathic treatment in thousands of patients in the long term and in various clinical conditions.

Concluding the book, the chapter “Pseudoskeptical and pseudoscientific strategies used in attacks on homeopathy” discusses pseudoskepticism and pseudoscience, describing the tell-tale signs of pseudoskepticism (bogus skepticism or pathological skepticism) in detail, which is a topic of fundamental importance for unmasking pseudo skeptics and pseudoscientists who systematically deny the vast amount of scientific evidence for homeopathy cited throughout the work.

Thus, despite the difficulties and limitations that exist in developing research in homeopathy, whether due to methodological aspects or the lack of institutional and financial support, the significant set of experimental and clinical studies described in the book is indisputable proof that “there is scientific evidence for homeopathy” and that “homeopathy is not placebo effect”, contrary to the falsely disseminated prejudice. However, new studies must continue to be developed to improve clinical practice and elucidate peculiar aspects of the homeopathic paradigm.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflicts of interest

The authors declare no conflicts of interest.

Marcus Zulian TeixeiraDepartamento de Psiquiatria, Faculdade de Medicina,Universidade de Sao Paulo, Sao Paulo, SP, Brazil

E-mail addresses: marcus@homeozulian.med.br, mzulian@alumni.usp.

(1) (PDF) Homeopathy is not placebo effect: proof of the scientific evidence for homeopathy in open access trilingual e-book. Available from: https://www.researchgate.net/publicatio ... ual_e-book