By Isabelle Chanel, Director, Research and Development, and Scientific and Medical Affairs, Boiron (France)
Research in homeopathy is a very wide subject and a real challenge for the pharmaceutical industry. We all know how efficient homeopathy is, but we still wonder how it works; what are the mechanisms of action? This is a mystery that we all would like to understand. We do not know yet but, work during the last decade has advanced our understanding.
Applied research in homeopathy is done in two large domains: basic/preclinical and clinical research. In basic and preclinical research, the main challenges are to study active ingredients 1) of various methods of high dilution (decimal, centesimal, Hahnemanian, Korsakovian, etc.), and 2) from a wide diversity of raw material (chemical, animal, vegetable, biological). In clinical research, the challenge is due to homeopathy being an individualized therapy; this makes it very difficult to run standard and repeated clinical studies on large groups of patients.
In basic research, we try to understand the physicochemical properties of homeopathic dilutions. The dynamization is studied and we explore the physical, chemical, or biological mechanism of action.
Dynamization is a key step in the manufacturing process for homeopathic solutions. Dynamization is essential to differentiate homeopathic solutions from neutral solutions or simply diluted solutions.1,2 It has already been demonstrated that a simply diluted solution does not have the same biological activity as a dynamized solution at each dilution step.3,4
We also know from very recent work, the physiochemical properties of homeopathic dilutions are very specific. Homeopathy is controversial because it relies on highly dilute medicines (also known as high homeopathic potencies or HHP) beyond the theoretical Avogadro/Loschmidt limit. Recent published studies using nuclear magnetic resonance (NMR) relaxation revealed the involvement of nanobubbles and/or nanoparticles and/or nanometric superstructures in high potentizations. Nano Tracking Analysis (NTA) demonstrated the presence of particles in HHPs. With scanning electronic microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), researchers observed an ionic diversity common to all preparations including HHPs. We observe significant differences in the relative quantity of each ion between different homeopathic dilutions and controls. Fourier transformation of infrared spectroscopy (FTIR) shows that the molecular composition is that of carbonates — primarily sodium bicarbonate. The homeopathic medicines do contain material with a specific ionic composition — even in HHPs diluted beyond the theorelical Avogadro/Loschmidt limit. This specificity can be attributed to the manufacturing process.5
We now have many studies that demonstrate the biological activity of homeopathic dilutions. A 2021 published study demonstrates that Gelsemium homeopathic dilutions increases adenosine triphosphate (ATP) synthesis which improves mitochondrial cell respiration, and activates cell development — having the same effect as never growth factor (NGF) exposure.6 Another study highlights the biological action of homeopathic dilutions of Arnica montana, Arsenicum album, and Lachesis mutus on cell models. This study highlights the anti free radical effect of these homeopathic dilutions in a microglial cell model, that oxidative stress is a well-known marker that could explain the anti-inflammatory properties of these strains.7
Another study shows that the homeopathic strain anas barbaraie hepatis et cordis extractum exhibits an anti-inflammatory effect by decreasing the oxidative stress induced by an inflammatory process in a microglial cell model.
This study also showed that strain acted quickly on the elasticity of microglial cells and leads to reorganization of the cell cytoskeleton by increasing the quantity of actin.8
The research database now contains a robust list of many studies with replication that demonstrate the biological action of homeopathic dilutions. All these studies provide elements to start understanding the mechanism of action but it is just the beginning. More work is needed to clarify the mystery of “how it works.” This type of research will greatly benefit from improvements in analytical precision, enabling detection at lower and lower levels.
On the clinical side, we now have promising evidence that demonstrates the power of homeopathy. A clinical study published in 2020 and performed by Professor Frass of the Medical University of Vienna and its team demonstrates that an individualized homeopathic treatment, in addition to an anti-cancer treatment, leads to a statistically significant improvement in the quality of life of patients with lung cancer and positive impact on their survival. This study is a very high-quality study; it is a double-blind study, performed in different centers, allowing for a more realistic sample representative and the placebo group also had consultation with a homeopath. It evaluates the quality of life with two different specialized questionnaires and allows direct evaluation of homeopathy on patient survival.9
Last but not least, “EPI3” is a large observational study conducted in France in 2007 which showed that the evolution of patients’ state of health when consulting with a homeopathic general practitioner is comparable to those consulting with a conventional general practitioner. The study also showed the patients seeing a homeopath took two to three times less conventional medication. This study was evaluated by Professor Yola Moride, an expert in pharmacoepidemiology who assessed the “methodological quality” of the EPI3 study. Professor Yola Moride confirmed the representativeness of the results at the national level. Adjustment, using appropriate statistical techniques, of the descriptive data of general practitioners and patients can lead to generalization of the results. Professor Moride confirmed the validity of the selection process for doctors and patients included with rigorous selection of doctors and patients. About 80 percent of the patients in the study completed the 12-month follow-up. The expert confirmed the data quality with results obtained using validated, disease-specific scales and instruments and the statistical methods with statistical analyzes following good observational research practices.10
There is no doubt that homeopathy is a powerful therapy that requires further research to understand the mechanisms of action and demonstrate its effectiveness in many pathologies. Running clinical studies remains a challenge because of the individualization of the treatment. Approaches using what we call Real-World Data (RWD) and Real-World Evidence (RWE) could definitely be a great support to demonstrate and validate treatment for many current pathologies once these methodologies are recognized by health authorities. Real Word Data are usually collected using electronic register of health insurance and start delivering proof of evidence of how homeopathy can help, for instance in supportive care in oncology11 in decreasing adverse events. Real World Evidence could easily benefit in adding homeopathy clinical cases collected by homeopathic doctors or practitioners as described in the clinical guidelines of the Homeopathic Pharmacopeia of the United States. Harmonized efforts from homeopathic laboratories with focus on some key pathologies (i.e., sinusitis, insomnia, migraine) would definitely help to further demonstrate the effectiveness of homeopathic medicine, which remains one of the safest classes of drug.
About the Author: Isabelle Chanel is Director, Research and Development, and Scientific and Medical Affairs, Boiron France. She has been involved with the development of homeopathic drug products for more than 20 years. Ms. Chanel has been a member of the Homeopathic Pharmacopeia of the United States since 2017, participating in its Council on Pharmacy and its Standards and Controls Committees. She earned her chemical engineering degree from The Chemical and Physical School of Lyon and a master’s degree in analytical chemistry from Lyon University.
- Demangeat JL. Gas nanobubbles and aqueous nanostructures: The crucial role of dynamization. Homeopathy. 2015;104(2):101–115.
- Van Wassenhoven M, Goyens M, Henry M, et al. Nuclear magnetic resonance characterization of traditional homeopathically manufactured copper (cuprum metallicum) and plant (gelsemium sempervirens) medicines and controls. Homeopathy. 2017 Nov;106(4):223–239.
- Betti L, Trebbi G, Kokornaczyk MO, Nani D, et al. Number of succussion strokes affects effectiveness of ultra-high-diluted arsenic on in vitro wheat germination and polycrystalline structures obtained by droplet evaporation method. Homeopathy. 2017 Feb;106(1):47–54.
- Kokornaczyk MO, Würtenberger S, Baumgartner S. Impact of succussion on pharmaceutical preparations analyzed by means of patterns from evaporated droplets. Sci Rep. 2020 Jan 17;10(1):570. doi: 10.1038/s41598-019-57009-2. PMID: 31953459; PMCID: PMC6969209.
- Van Wassenhoven M, Goyens M, Dorfman P, Devos P. Particle characterisation of traditional homeopathically manufactures medicine cuprum metallicum and controls. Int J High Dilution Res. 2021;20(4):11–28.
- Lejri, Imane & Grimm, Amandine & Trempat, Pascal & Boujedaini, Naoual & Eckert, Anne. Gelsemium low doses increases bioenergetics and neurite outgrowth. (2021) 10.21203/rs.3.rs-377125/v1.
- Paumier A, Verre J, Tribolo S, Boujedaini N. Anti-oxidant effect of high dilutions of arnica montana, arsenicum album, and lachesis mutus in microglial cells in vitro. Dose-Response. 2022 Jun 29;20(2):15593258221103698. doi: 10.1177/15593258221103698. PMID: 35795190; PMCID: PMC9251990.
- Runnel G, Paumier A, Verre J, Catte A, Tribolo S, Chlasta J, BoujeDaini N. Action of ultra-low dose medicine on oxidative stress and cell stiffness of microglial cells in vitro with actin filaments reorganization. International Journal of Pharmaceutical Research. 2022.
- Frass M, Lechleitner P, Gründling C, Pirker C, Grasmuk-Siegl E, Domayer J, Hochmair M, Gaertner K, Duscheck C, Muchitsch I, Marosi C, Schumacher M, Zöchbauer-Müller S, Manchanda RK, Schrott A, Burghuber O. Homeopathic treatment as an add-on therapy may improve quality of life and prolong survival in patients with non-small cell lung cancer: A prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter study. Oncologist. 2020 Dec;25(12):e1930-e1955. doi: 10.1002/onco.13548. Epub 2020 Nov 7. Erratum in: Oncologist. 2021 Mar;26(3):e523. PMID: 33010094; PMCID: PMC8108047.
- Moride Y. Methodological considerations in the assessment of effectiveness of homeopathic care: A critical review of the EPI3 study. Homeopathy. 2021 Sep 14. doi: 10.1055/s-0041-1732335. Epub ahead of print. PMID: 34521145.
- Medioni J, Scimeca D, Lopez Marquez Y, Leray E, Dalichampt M, Hoertel N, Bennani M, Trempat P, Boujedaini N. Benefits of homeopathic complementary treatment in patients with breast cancer: A retrospective cohort study based on the French nationwide healthcare database. To be published in Clinical Breast Cancer.