Homeopathy 2018; 107(04): 244-263
Nanoparticle Characterisation of Traditional Homeopathically Manufactured Cuprum metallicum and Gelsemium sempervirens Medicines and Controls
Michel Van Wassenhoven, European Committee for Homeopathy, Brussels, Belgium
Martine Goyens, Pharmaceutical Association for Homeopathy, Wépion, Belgium
Etienne Capieaux, PhytoCap, Bioengineering, Namur, Belgium
Philippe Devos, Unio Homoeopathica Belgica, Evergem, Belgium
Pierre Dorfman, Centre Européen d'Informatique et d'Automation, Brussels, Belgium
Funding This study was funded by private donations from patients and doctors, with corporate support from UNIO HOMOEOPATHICA BELGICA (Belgian MD Homeopathic Union).
Abstract
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.
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https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0038-1666864Excerpts:
"Recent studies indicate that homeopathically prepared medicines (HMs) contain source nanoparticles (NPs),[1] [2] [3] [4] silicates,[3] [5] [6] and other, less well-characterised structures.[7] Recent systematic review work on randomised controlled trials confirmed that the medicines prescribed in individualised homeopathy may have small, specific, treatment effects.[8] [9] Nevertheless, sceptics continue to insist that HMs are mere placebos containing no active material in any form.[10]
"This debate about plausibility and evidence[11] can be settled by fundamental research. Some people have focused on the dilution of bulk source material beyond the Avogadro's number and have ignored the fact that the actual manufacturing process is more than simple dilution[11]— it involves step-by-step potentisation (for water-soluble material), also called a ‘dilution-dynamisation’ process, which is described in the European pharmacopoeia.[12] The potentisation process is performed here using a certified machine which normally provides 100 calibrated vertical shocks at each dilution. The dilution process may be 1 part of material for 9 parts of solvent (dHahnemannian or xH potency) or 1 part of material for 99 parts of solvent (cH or cKorsakov potency). The containers are always of pharmaceutical grade soda-lime-silicate glass ISO-719, ISO4802-1, Ph-Eur 3.2.1. For Hahnemannian potencies, a new container is used at each step, whilst Korsakov potencies are prepared within the same container at each dilution step.
"Nanotechnology researchers have begun to recognise similarities between the traditional manufacturing techniques of homeopathy using crude, mechanical abrasion and the top-down approaches for making nanostructures from insoluble source materials used in modern nanotechnology.[1] [2] [4] The authors, using transmission electron microscopy and inductively coupled plasma atomic emission spectroscopy (ICP-AES), found irregularly shaped poly-dispersed source metal particles, in concentrations ranging from picograms to nanograms per millilitre, in six different commercially made metal HMs including copper.
"Previous publications[7] [13] [14] [15] using nuclear magnetic resonance (NMR) relaxation have revealed the involvement of nanobubbles and/or NPs and/or nanometric superstructures in high potentisations.
"The purpose of this exploratory study is to replicate and extend the characterisation of colloidal NP in homeopathically prepared Cuprum metallicum (copper source) following good pharmaceutical practice (GPP) in 4cH, 5cH, 6cH, 7cH, 30cH and 200cK potencies compared with a solvent control, potentised lactose control, simply diluted copper control and other controls (silver, silica and potassium chloride) and to verify whether the specific NPs can be identified in dH, cH and cK potentisations from a soluble mother tincture (MT) of a plant (Gelsemium), compared with solvent controls, simply diluted medicines and others."
[Discussion]
"Following the European pharmacopoeia,[12] to avoid precipitates, first dilutions of soluble MT must be prepared using the same alcohol concentration as the MT, but alcohol is not required for higher dilutions when producing homeopathic medicines."
"All Korsakov intermediate preparations are similarly prepared using pure water, and alcohol is added only for the final dynamisations. The homeopathic manufacturing tradition expects that the homeopathic information is carried by the water and not by the alcohol."
"Particles were present even in the highest dilutions, in low quantities but clearly measurable. There was a clear difference in all NTA aspects from the potentised water control, prepared in PET containers, which contained only a few particles of a large size distribution."
"The idea that homeopathic medicines are non-material, propounded by both opponents of homeopathy and by traditional homeopathic practitioners, cannot be maintained in view of these findings. Science is measurement; measurements are facts that cannot be denied. Nevertheless, the presence of these few particles does not allow us to conclude that the effect of homeopathy is due to a classical molecule–receptor interaction. Given that the final product (impregnated pills, globules, granules etc.) contains only a very small quantity of the HMs in question, a different pathway is much more likely. To verify this assertion, other methodologies, such as NMR[15] and/or electro-photonic analysis, are required. It is notable that the mean particle sizes measured by NTA (between 100 and 170 nm) are consistent with the size predictions of quantum coherence domains generated during the potentisation process.[41]"
"The great variation in the size of particles ([table 7]) is an indication of the complex shapes of particles in homeopathic medicines...In a future article, we intend to discuss all these findings in the context of the wider literature, adding the new NMR results.[15] We are aware that these findings are somewhat startling, illustrating the impossibility of detecting any major elements from the original stock (copper, silver, gelsemine, etc.) and showing that the remedy specificity derives not from a single element but from very small, complex particles."
"The number of particles by frame (NTA) in Cuprum 30 cH prepared in PET containers is significantly higher than in dynamised water in PET containers (75% higher). What is the origin of these particles? For a same manufacturing process, this difference can only derive from the material (3 cH triturated Cuprum) added to the water for further dynamisations."
"The specificities of each preparation (different starting material, specific manufacturing process, level of dilution/dynamisation) are identified. The common factors to all preparations are also known: containers, passivation process, measurement techniques, quality of water and ambient air.
"Soda glass containers are leaching particles; surely more than a PET container (see potentised water manufacturing line in soda glass versus PET, [table 8]). Ambient air mix may play a role considering lactose, used for the trituration. In pharmaceutical-grade lactose monohydrate, some heavy metals are tolerated (Pb = 0.5 ppm, As = 5 ppm, Cd = 1 ppm, Hg = 5 ppm) and non-toxic elements may not exceed 2% (glucose and other impurities). It must be noted that none of these elements was identified in the collected dry material."
"As such, the presence of carbon and oxygen is expected (from the lactose), but the oxygen is in a higher proportion than would be expected from lactose. This can be explained by the trituration process. The other elements may partially originate from the triturated lactose, air contaminants, water contaminants and containers but their percentages and especially their variability question this line of argument. PET containers may leach but the quantities of material are non-significant (see dynamised water in PET).
"Another origin may be the measurement devices. As example, the concentration is required before elements can be identified using the EDX process...As such, theoretically, we can expect more particles from the lyophilisation flask than other preparations even if a release of particles, as occurs during preparation in soda glass containers, is not expected at a significant level at this step prior to the EDX measurements because DURAN glass is more stable than any other glass."
"Lastly, a possible factor may be gas contamination from the ambient air (CO2, for example) or by hydrophobic dust (such as carbon) which is very difficult to eliminate by washing containers with water before passivation."
"The chemistry of the materials, determined by EDS, shows that they are not composed only of molecular compounds from the original MT. We did not find copper or silver in the samples, but nevertheless each of the samples, stocks and/or dilution/dynamisations has a specific composition, and the proportions of the various atoms resulted in a specific chemical profile. Because of the absence of any particles in the pure deionised water used (NTA), the presence of these elements can only be explained by an interaction between the original stock, the glass containers used, ambient air and the deionised water. Some of them may derive from the stock itself, whilst others could be extracted from the glass due to the glass-aggressive nature of deionised water. The deionised water's aggressiveness could be tempered, more or less, by the addition of the starting material or previous dilution. The step-by-step dilution/dynamisation process plays a significant role because particles are also produced in deionised potentised aqua pura 30 cH; in this case, this can only be due to a reaction between the glass and the water. On the other hand, the specificities of the different samples clearly illustrate the persistent impact of the original stock throughout the dilution or potentisation process. A simple dilution is not a potentisation, and there is a difference between the cH, cK potentisation processes and controls."
"Whilst the dilution factor is part of the dynamisation process, the dynamisation itself produces detectable changes in the size, atomic composition and shapes of the resulting particles. It is important to stress the fact that we recovered from the simply diluted preparations about twice the residual dry material as from a comparable potentised medicine. The dynamisation process not only reduces the amount of material but also induces specific chemistry, shapes and sizes. These important differences justify further studies into the behaviour of the solvent surrounding these specific particles. Some authors[43] [44] have reported similar observations: they have identified electrically charged and stable water-clusters or dissipative structures in liquid water of low energy content."
"To address the problem of plausibility[11] of homeopathic medicines, more pharmacological studies are needed. The present measurements justify further research and demonstrate the importance of GPP and of excellent quality control for the MT. It also opens new perspectives for further research areas and for alternative explanations of the mechanism of action of homeopathic medicines. Research on homeopathic medicines must not remain anecdotal but should be integrated into the pharmaceutical training of future pharmacists. The DynHom project must continue and carry out more systematic particle measurements, as has already taken place with the NMR study.[15]"
"Using a step-by-step dilution or potentisation process, NTA findings revealed the presence of particles in all samples (except for pure water), even at the highest level of dilution; quantities were very low but measurable. The measurements showed large differences in particle quantities, mean particle sizes and SDs of the mean sizes between manufacturing lines of different starting material.
"At the end of the lyophilisation process, free dry residues were collected and weighed. There was more material in simply diluted preparations than in samples potentised to the same level of dilution, and more than in the potentised pure water. The Gelsemium yielded the largest quantity of material (36 times more than from copper at the same potentisation, 30 cH). The existence of this material demonstrates that the step-by-step process used (dynamised or not) does not match with the theoretical expectations in a dilution process."
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Comments: these results do not provide any support to homeopathy. There is material found in the highly diluted samples, but it does not contain the original substance, suggesting it is something introduced from the materials and processes used to make the dilutions. But if materials are introduced throughout the process, why is much less obtained in the case of pure water?
The amount of solid material recovered from a sample does not seem to change with increasing dilution, in support of the idea that impurities are being introduced all along the way. For example, gelsemium had 42 ug for a 4cH dilution, 36 ug for 30 cH, and 30.5 for 200cK (corresponding to 10^8, 10^60, and 10^400-fold dilutions, respectively).
On the other hand, the results are peculiar because the material in the diluted samples differs with different starting materials, and one would think that any initial effect on what impurities are introduced would get weaker with each successive dilution.
