Nanoparticle Characterisation of Traditional Homeopathically Manufactured Cuprum metallicum and Gelsemium sempervirens Medicines and ControlsFunding This study was funded by private donations from patients and doctors, with corporate support from UNIO HOMOEOPATHICA BELGICA (Belgian MD Homeopathic Union).
24 January 2017
14 May 2018
25 August 2018 (eFirst)
Background Homeopathy is controversial due to its use of very highly diluted medicines (high potencies/dynamisations).
Methods We used a multi-technology approach to examine dilutions of two commonly used homeopathic medicines: an insoluble metal, Cuprum metallicum, and a soluble plant tincture, Gelsemium sempervirens, for the presence of nanoparticles (NPs) of original substance. The homeopathic medicines tested were specially prepared, according to the European pharmacopoeia standards. We compared the homeopathic dilutions/dynamisations with simple dilutions and controls.
Results Using Mass Spectrometry (Single Particle-Inductively Coupled Plasma-Mass Spectrometry) and Dynamic Light Scattering (DLS) we could not find the expected copper in the 4cH potentisation and could not confirm the results previously obtained by Chikramane et al (2010). For Gelsemium medicines, using sensitive chromatography (HPLC-UV) up to a dilution level of 6 dH (3cH = dilution 10e-6), there was no significant difference in alkaloid content between a simple dilution and a homeopathic potency.
For higher potentisations, however, NP tracking analysis findings revealed the presence of particles in all samples (except for pure water). The measurements showed large differences in particle quantities, mean particle sizes and standard deviations of the mean sizes between manufacturing lines of different starting material.
There was always more material in potentised medicines than in potentised pure water. Gelsemium yielded the largest quantity of material (36 times more than that from copper at the same potentisation, 30 cH). The shapes and the chemical composition of the material are differentiable between different medicines and controls.
Conclusion Potentisation influences specifically the nature of NPs detected. This material demonstrates that the step-by-step process (dynamised or not) does not match with the theoretical expectations in a dilution process. The Avogadro/Loschmidt limit is not relevant at all. It was not possible to reproduce the findings of Chikramane et al (2010) using inductively coupled plasma-mass spectrometry with copper. Copper NPs could not be detected at 4cH and above.
Keywordsnanoparticles - Cuprum metallicum - Gelsemium sempervirens - Silicea terra - Argentum metallicum - Kalium muriaticum - lactose - water - homeopathy - potentisation - dynamisation - pharmacology - mass spectrometry - high-performance liquid chromatography - dynamic light scattering - nanoparticle tracking analysis - zeta-potential - scanning electron microscopy
• The nature of homeopathic medicines even in highest dilutions is identified using modern measurement methods.
• The presence of material in high-diluted homeopathic medicines invalidates the Avogadro/Loschmidt limit for homeopathic potentisations.
• Starting material is not identifiable in high homeopathic potentisations.
- 1 Chikramane PS, Kalita D, Suresh AK, Kane SG, Bellare JR. Why extreme dilutions reach non-zero asymptotes: a nanoparticulate hypothesis based on froth flotation. Langmuir 2012; 28: 15864-15875
- 2 Chikramane PS, Suresh AK, Bellare JR, Kane SG. Extreme homeopathic dilutions retain starting materials: a nanoparticulate perspective. Homeopathy 2010; 99: 231-242
- 3 Upadhyay RP, Nayak C. Homeopathy emerging as nanomedicine. Int J High Dilution Res 2011; 10: 299-310
- 4 Bell IR, Muralidharan S, Schwartz GE. Nanoparticle characterisation of traditional homeopathically-manufactured silver (Argentum Metallicum) medicines and placebo controls. J Nanomed Nanotechnol 2015; 6: 311
- 5 Ives JA, Moffett JR, Arun P. , et al. Enzyme stabilization by glass-derived silicates in glass-exposed aqueous solutions. Homeopathy 2010; 99: 15-24
- 6 Cartwright S. Pyridinium-N-phenolates as molecular probes of serially diluted and agitated solutions: preliminary results. Homeopathy 2014; 103: 65
- 7 Demangeat JL. Gas nanobubbles and aqueous nanostructures: the crucial role of dynamization. Homeopathy 2015; 104: 101-115
- 8 Mathie RT, Lloyd SM, Legg LA. , et al. Randomised placebo-controlled trials of individualised homeopathic treatment: systematic review and meta-analysis. Syst Rev 2014; 3: 142
- 9 Mathie RT, Van Wassenhoven M, Jacobs J. , et al. Model validity and risk of bias in randomised placebo-controlled trials of individualised homeopathic treatment. Comp Ther Med 2016; 25: 120-125
- 10 Editorial (2005). The end of homeopathy. Lancet 2005; 366: 690
- 11 Rutten L, Mathie RT, Fisher P, Goossens M, Van Wassenhoven M. Plausibility and evidence: the case of homeopathy. Med Health Care Philos 2013; 16: 3/525-532
- 12 European Pharmacopoeia Online 8.2. 2014. Available at: http://online6.edqm.eu/ep801/mobile/
- 13 Demangeat JL. NMR water proton relaxation in unheated and heated ultrahigh aqueous dilutions of histamine: evidence for an air-dependent supramolecular organisation of water. J Mol Liq 2009; 144: 32-39
- 14 Demangeat JL. Nanosized solvent superstructures in ultramolecular aqueous dilutions: twenty years' research using water proton NMR relaxation. Homeopathy 2013; 102: 87-105
- 15 Van Wassenhoven M, Goyens M, Henry M, Capieaux E, Devos P. Nuclear Magnetic Resonance characterization of traditional homeopathically manufactured copper (Cuprum metallicum) and plant (Gelsemium sempervirens) medicines and controls. Homeopathy 2017; 106: 223-239
- 16 Tsukihara T, Aoyama H, Yamashita E. , et al. Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A. Science 1995; 269: 1069-1074
- 17 Hodiamont. Homéopathie et Physiologie. Baillère JB. , ed. Paris: Similia; 1983
- 18 Hahnemann S. . (1828). Chronic Diseases. Schmidt & Kunzli eds. South Asia Books; 2005
- 19 Allen T. Encyclopedia of Pure Materia Medica. New York: Boericke & Tafel; 1879
- 20 Bradford T. Index of Homeopathic Provings. New Delhi: B Jain Publishers; 2000
- 21 Duke J, Hughes R. Cyclopaedia of Drug Pathogenesy. London: B Jain Publishers; 1891
- 22 Allen HC. Allens Keynotes. New Delhi: B Jain Publishers; 2000
- 23 Dorfman P, Guillemain J, Nevy P, Tetau M. Double-blind drug pathogenesy of Cuprum metallicum 30CH. Cahiers de Biothérapie 1987; 93: 47-56
- 24 Mahata CR. Dielectric dispersion studies of some potentised homeopathic medicines reveal structured vehicle. Homeopathy 2013; 102: 262-267
- 25 Betello CF. Antioxidante effect in vitro of the homeopathic medicine Arsenicum album, Cuprum metallicum, Manganum and Zincum metallicum. Thesis Faculdade de Ciências da Saude de São Paulo, Brazil; 2002
- 26 Smits T. Inspiring Homeopathy: Treatment of Universal Layers. ISBN 9789076189000; United States: Emryss; 2013
- 27 Van Wassenhoven M. First line medicine – Clinical Verification – Verification of homeopathic symptoms. Cuprum metallicum. ISBN 978-2-87491-003-6; New Delhi: B Jain Publishers; 2008
- 28 Boericke W, Boericke OE. Homeopathic Materia Medica. ISBN 0766183882; Motilal Banarsidass; 1927
- 29 Santini R, Tessier M, Bellon P. First experimental arguments in favour of the effect of very weak doses of copper on digestive motricity in mice and rabbits. In: Ultra Low Doses. London, UK: Taylor & Francis; 1991: 3-10
- 30 Hariveau E, Nolen P, Holtzscherer A. A study of the effectiveness of ultra low doses of copper in the treatment of hemodialysis-related muscle cramps. RCT. In: Doutremepuich C. , ed. Ultra Low Doses. London: Taylor & Francis; 1991: 145-149
- 31 Vermeulen F, Johnston L. Plants. Homeopathic and Medicinal Uses from a Botanical Family Perspective. Glasgow, Scotland: Saltire Books. ISBN 978-0-955-90655-8; 2011
- 32 Mishra N, Muraleedharan KC, Paranjpe AS, Munta DK, Singh H, Nayak C. An exploratory study on scientific investigations in homeopathy using medical analyzer. J Altern Complement Med 2011; 17: 705-710
- 33 Marzotto M, Olioso D, Brizzi M, Tononi P, Cristofoletti M, Bellavite P. Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens. BMC Complement Altern Med 2014; 14: 104
- 34 Dimpfel W, Biller A. In vivo and in vitro neurophysiological findings in the rat in the presence of Coffea D6, Gelsemium D4 and Veratrum D6 extracts. Scientific Framework of Homeopathy; 2014. LMHI. Available at: http://www.lmhi.org/Article?menuId=13&subMenuId=41
- 35 Meyer L, Boujedaini N, Patte-Mensah C, Mensah-Nyagan AG. Pharmacological effect of gelsemine on anxiety-like behavior in rat. Behav Brain Res 2013; 253: 90-94
- 36 Van Wassenhoven M. First line medicine – Clinical verification – Verification of homeopathic symptoms. ISBN 978-2-87491-003-6; New Delhi: B Jain Publishers; 2008
- 37 Magnani P, Conforti A, Zanolin E, Marzotto M, Bellavite P. Dose-effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice. Psychopharmacology (Berl) 2010; 210: 533-545
- 38 Bellavite P, Conforti A, Marzotto M. , et al. Testing homeopathy in mouse emotional response models: pooled data analysis of two series of studies. Evid Based Complement Alternat Med 2012; 2012: 954374
- 39 Dorfman P, Tetau M. Applications cliniques de la recherche pharmacologique. Cahiers de Biothérapie n°125; Eds Similia Paris, France; 1993
- 40 Paris A, Schmidlin S, Mouret S. , et al. Effect of Gelsemium 5CH and 15CH on anticipatory anxiety: a phase III, single-centre, randomized, placebo-controlled study. Fundam Clin Pharmacol 2012; 26: 751-760
- 41 Bono I, Delgiudice E, Gamberale L, Henry M. Emergence of the coherent structure of liquid water. Water 2012; 4: 510-531
- 42 Albrigo LG, Szafranck RC, Childers NF. The role of Molybdenum in Plants and soils. Climax Molybdenum Co., Supplemental volume 1966. Available at: http://www.climaxmolybdenum.com/ Phenix USA
- 43 Lo S, Geng X, Gann D. Evidence for the existence of stable-water-clusters at room temperature and normal pressure. Phys Lett A 2009; 373: 3872-3876
- 44 Elia V, Germano R, Napoli E. Permanent dissipative structures in water: the matrix of life? Experimental evidences and their quantum origin. Curr Top Med Chem 2015; 15: 559-571
- 45 Peck R, Olsen C, Devore JL. . (2008). Introduction to Statistics and Data Analysis, 3rd ed. Available at: https://www.cengage.co.uk/