The Journal of Alternative and Complementary Medicine Vol. 25, No. 9 pp. 890-901
Physicochemical Investigations of Homeopathic Preparations: A Systematic Review and Bibliometric Analysis—Part 2Alexander Tournier (1,2), Sabine D. Klein (1), Sandra Würtenberger (3), Ursula Wolf (1), and Stephan Baumgartner (1,4,5)
1 Institute of Complementary and Integrative Medicine, Faculty of Medicine, University of Bern, Bern, Switzerland.
2 Water Research Lab, Heidelberg, Germany.
3 Scientific and Regulatory Affairs, Hevert-Arzneimittel GmbH & Co. KG, Nussbaum, Germany.
4 Society for Cancer Research, Arlesheim, Switzerland.
5 Institute of Integrative Medicine, Faculty of Health, University of Witten/Herdecke, Witten, Germany.
Abstract
Objectives: In Part 1 of the review of physicochemical research performed on homeopathic preparations the authors identified relevant publications of sufficient reporting quality for further in-depth analysis. In this article, the authors analyze these publications to identify any empirical evidence for specific physicochemical properties of homeopathic preparations and to identify most promising experimental techniques for future studies.
Methods: After an update of the literature search up to 2018, the authors analyzed all publications in terms of individual experiments. They extracted information regarding methodological criteria such as blinding, randomization, statistics, controls, sample preparation, and replications, as well as regarding experimental design and measurement methods applied. Scores were developed to identify experimental techniques with most reliable outcomes.
Results: The publications analyzed described 203 experiments. Less than 25% used blinding and/or randomization, and about one third used adequate controls to identify specific effects of homeopathic preparations. The most promising techniques used so far are nuclear magnetic resonance (NMR) relaxation, optical spectroscopy, and electrical impedance measurements. In these three areas, several sets of replicated high-quality experiments provide evidence for specific physicochemical properties of homeopathic preparations.
Conclusions: The authors uncovered a number of promising experimental techniques that warrant replication to assess the reported physicochemical properties of homeopathic preparations compared with controls. They further discuss a range of experimental aspects that highlight the many factors that need to be taken into consideration when performing basic research into homeopathic potentization. For future experiments, the authors generally recommend using succussed (vigorously shaken) controls, or comparing different homeopathic preparations with each other to reliably identify any specific physicochemical properties.
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https://www.liebertpub.com/doi/10.1089/acm.2019.0064Excerpts:
"However, specific efficacy and the mode of action of homeopathic remedies—especially in high dilution—is still the subject of scientific debate.
"A major challenge of homeopathic basic research is to decode any physicochemical mode of action. The aim of this review project was to contribute to this effort through a systematic literature search and a thorough evaluation of the state of research in this field."
"In the present, second article, the authors report on a methodological analysis of the investigations in the different physicochemical research areas...The aim was to identify any empirical evidence for specific physicochemical properties of homeopathic preparations, and to identify most promising experimental techniques for future studies."
"Most experiments used plain (unsuccussed) potentizing medium as control, whereas less than one third used potentized medium (Table 2); 23% of experiments used more than one control. Twenty-three percent of experiments reported blinding and 21% reported randomization. Only 15% of the experiments reported measurements of multiple independent sample production lots. Most of the experiments (59%) did not report the use of statistics to analyze the data, whereas 28% reported use of inferential statistics."
"A total of 192 different substances were investigated. The most used potentized substance was Natrium muriaticum (sodium chloride), followed by 2.4-dichlorophenoxyacetic acid, Arnica montana, sulfur, Nux vomica, and Silicea (Table 4).
"The most frequently used measurement techniques were electrical impedance, spectroscopy followed by nuclear magnetic resonance (NMR) (Table 5)."
"If we look at the best experiments, defined as those that used blinding, randomization, and inferential statistics, we find overall 24 experiments, of which 79% reported differences between homeopathic preparations and controls (Table 6). Of those, 10 fulfilled a further two methodological criteria (use of succussed controls and use of independent lot production), 80% of which reported differences between homeopathic preparations and controls."
"For the purposes of this review, we define a replication as an experiment that used the same investigative technique to measure the same physicochemical properties of homeopathic potencies made of the same substances. Note that this is different from a reproduction where the same instrument and potencies would have to be used, along with the same statistical analysis, experiment protocol, and materials."
(Discussion section)
"A major question that came up during this review is how to define the most appropriate controls for homeopathic preparations in physicochemical measurements. We can distinguish two main classes of controls: (1) plain (unsuccussed) solvent or diluted (but not succussed) homeopathic samples and (2) potentized or succussed (vigorously shaken) solvent. It is quite evident that succussion of a fluid in ambient air leads to a number of effects such as formation of air bubbles of different size with differential lifetimes, increased dissolution of air components (N2, O2, CO2) in the fluid, increased dissolution of potentization vessel wall material (Si, B, Na, K etc.), and maybe cavitation effects.144 These processes may lead to further consequences such as increased oxidative processes (because of O2 dissolution), changes in pH (because of CO2 dissolution and acid formation), changes in nuclear magnetic relaxation (O2 as relaxation agent), increased silica-hydrogel formation (because of increased Si dissolution), radical formation (because of cavitation), and potentially other effects."
"Considering the hypothesis that succussion leads to some information transfer of the substance potentized to the potentization medium, the question arises what happens when pure medium is potentized as control sample (e.g., potentized water). One could speculate that the potentization process is amplifying some random information. This would lead to a situation where samples with specific information (homeopathic preparations) would be compared with samples with random information (potentized water as control). In this sense potentized medium (and by extension succussed medium too) might not to be the best controls possible as they could introduce a random element.
"On the contrary, one can argue that it would not be wise to compare homeopathic preparations with each other in case the measurement method used is not able to distinguish the putative homeopathic structures. Because the nature of the homeopathic structures is not known yet, it cannot be decided at present if a given measurement method is able or not to distinguish the presumed structures.
"We therefore recommend in future investigations the use of two types of controls: (1) potentized solvent and (2) other homeopathic preparation(s). The use of several homeopathic samples increases the probability to identify different structures. Furthermore, if possible, we recommend the additional use of (3) unsuccussed and (4) succussed control samples that would allow determining the effect of pure succussion."
"Most of the studies neither used blinding nor randomization. This is not entirely unusual in physicochemical research where one usually does not expect experimenter effects. Most of conventional research does not invoke blinding on such experiments for that very reason. Giving the history and heated debate surrounding homeopathy, we recommend implementing blinding and randomization protocols in future investigations to ensure that experimenters do not have any effect on the results.
"Rather worrying is the lack of use of proper statistical tools. Part of the problem here is that many of the studies are quite dated and statistical tools were often not used at that time. Another effect is that many experiments such as in spectroscopy have been rather descriptive and therefore did not use statistical tools. Now, again given the controversy in the field, there is a great need for proper statistical methods to be implemented, so as to quantify the degree of uncertainty in the results and to avoid Type I and Type II errors.
"We recommend the implementation of systematic negative control (SNC) experiments on a regular basis. SNC experiments are full experiments with identical design and evaluation as experiments with homeopathic preparations, but all samples are either from the same source material (e.g., plain potentization medium) or consist of potentized medium, prepared analogously as the homeopathic samples.146 Depending on the design of the experiments, systematic positive control (SPC) experiments may also be a valid approach, consisting of the same sample (either a positive control or a homeopathic preparation), independently prepared in the number of samples assessed in the 'true' experiments. SNC and SPC experiments are excellent scientific tools to evaluate the stability of a given experimental system, to identify any systematic error, and to assess applicability of statistical models. In this review, only one investigation implemented SNC experiments."
"Looking at the results gathered in this review a number of experiments emerge as deserving further replication and exploration. First of all, NMR relaxation studies of potentized silica and histamine preparations have shown the most methodological rigor and the most promising results, demonstrating the ability to distinguish between potentized silica or histamine, and potentized controls. Of interest, potentized sulfur seems to be harder to distinguish from corresponding controls.
"Based on the available data, UV spectroscopy seems to be the second most interesting technique. With this experimental approach only, a formal meta-analysis over three independent experimental series yielded statistically significant differences between potencies of copper sulfate and succussed medium.
"Thermoluminescence on potentized lithium chloride seems to be the third promising technique, although it requires quite sophisticated and expensive equipment."
"The search criteria defined homeopathic preparations as having undergone succussion steps, as such a number of publications from the field of water research and of high-dilutions research were not included. In particular the work of Pollack on 'Exclusion Zone' (EZ) water, which is often cited as a possible line of enquiry for explaining homeopathy, did not fulfill the criteria and was not retained (for a overview of this field, the reader is referred to the book by Pollack: 'The Fourth Phase of Water'148). Similarly, the work of Konovalov and Ryzhkina on structures terms 'Nanoassociates' at ultralow dilutions, did not meet the criteria and was not retained (for more details the reader is referred to the review of the field by Konovalov and Ryzhkina149)."
