Jean-Louis Demangeat is a French scientist and physician, a Doctor of chemistry and nuclear medicine. For more than 30 years, Demangeat has devoted his research to the study of ultra-high dilutions (UHDs) of substances by nuclear magnetic resonance.
Dr. Jean-Louis Demangeat. Source
Having studied biochemical engineering, Dr. Demangeat began his scientific career in 1970 as an assistant in the Institute of Biophysics at the University of Strasbourg's Faculty of Medicine. In 1975, he received a doctorate in the physical chemistry of micromolecules. In 1982, Demangeat became a qualified specialist in the field of nuclear medicine. In addition, he has taught biophysics and medical physics, mathematics and thermodynamics at the University of Strasbourg Faculty of Medicine and Dentistry. Demangeat has conducted research into the biophysical aspects of protein and DNA interaction in eukaryotes. He has also conducted research in the field of nuclear cardiology. In 1991 Jean-Louis Demangeat was appointed Head of the Department of Nuclear Medicine at Hospital Haguenau in France, and began to devote more time to clinical and methodological work. Responsible for radiation safety in the hospital, he became interested in the effects of ionising and non-ionising radiation on people, and also in ultra-high dilutions of various substances and their possible mechanisms of effect on the body.
Demangeat qualified as a doctor in 1987. From this point on, Dr. Demangeat began to devote much of his time to using nuclear magnetic resonance (NMR) to study UHDs of substances. Dr. Jean-Louis Demangeat is the author of more than 200 scientific papers (1).
Since 1992, he has studied UHDs of silicon dioxide (2-6), manganese (3, 6), histamine (6, 7), arsenic and antiserum (blood serum containing antibodies) (8). He has also studied how much the properties of UHDs are affected by various solvents (4, 5), physical factors (heating, mechanical stirring or dynamisation), and the material of the vessels in which the UHD is produced and stored (5-8). It is worth noting that in all of the studies, special attention was paid to developing experimental design. The control series of experiments were prepared in a similar way to the experiments (and were even performed simultaneously) in order to eliminate errors. Several independent series of measurements were carried out, and the 'blind method' was used (the experimenter did not know which of the samples was experimental and which was the control until the end of the study). In Demangeat's experiments, it was possible to show the difference in the physical state of the UHDs compared to controls that did not initially contain solute by using the NMR method.
It is worthwhile mentioning the method used by Demangeat to study UHDs. Nuclear magnetic resonance (NMR) and proton magnetic resonance (PMR) are physical methods based on the phenomenon of atomic nuclei in the composition of the molecules of a sample placed in a magnetic field absorbing electromagnetic radiation. The condition for the use of PMR is the presence of a non-zero spin (nuclear magnetic dipole) in the nucleus of an atom. In an H2O water molecule, only 1H protons have a non-zero spin; therefore, the motion of the water molecule is 'visible' through the motion of its protons (6).
NMR research instrument
When hydrogen atoms are put into an external magnetic field, nuclei with magnetic moments pointing 'towards' or 'against' the field have different energies (are distributed over different energy states), and an energy transition from one state to another becomes possible, which is the physical basis of the NMR method. If the sample is now irradiated with electromagnetic radiation, then at a certain 'resonant' frequency, energy absorption is observed: the transition of the nuclei to a higher energy state when a quantum of electromagnetic radiation is absorbed.
The NMR spectrum is a graph showing the peaks of resonant frequencies. When the magnetic field is turned off, relaxation occurs - the nuclei return from an excited to a normal equilibrium state. For liquids such as water, this process takes 0.1-10 seconds (6). The return to the normal state can occur either through the thermal mechanism of exchange with neighbouring atoms or molecules (denoted by relaxation time T1) or the magnetic (denoted by relaxation time T2). The resonance frequencies and relaxation times are strongly influenced by the interactions between neighbouring protons (from a substance or solvent), giving complex spectra (with extended resonance peaks) which allow accurate analysis of the molecular structure, molecular dynamics and chemical exchange of protons (6, 9).
Demangeat considers studying the chemical and physical properties of the solvent the most promising field in UHD research. In this regard, PMR seems to be the preferred method: in alcohol or aqueous dilute solutions, the protons of water or ethanol are in quasi-constant maximum amounts, giving the optimal signal to noise ratio (9). By determining the T1 and T2 relaxation times (parameters characterising the movement and organisation of water molecules) using the PMR method, Demangeat investigates the degree of 'structuredness' of the solvent, depending on the degree of dilution. A decrease in the mobility of molecules and/or a higher structuring of water can be expressed through four criteria for PMR relaxation: 1) a decrease in T1, 2) a decrease in T2, 3) an increase in the T1/T2 ratio, 4) differing dynamics of T1 and T2. At the same time, Dr. Demangeat considers the latter two criteria the most sensitive and reliable.
Change in T1 relaxation time in histamine UHD (top) (7) and the T1/T2 ratio in silicon dioxide/lactose UHD (bottom) (5) depending on the degree of dilution. A linear increase in T1 and T1/T2 with an increase in the degree of dilution reflects a decrease in the mobility of water molecules and/or an increase in structuredness (left). After heating, this effect disappears (right).
Demangeat conducted his first experiments studying UHDs using silicon dioxide (SiO2) as the solute and brine (NaCl) as the solvent (dilutions from 10-6 to 10-30) (2, 6). A solution of silicon dioxide was obtained by initially triturating a solid with lactose, and as a result, we refer to UHDs of silicon dioxide and lactose in these experiments. Dr. Demangeat subsequently repeated these experiments, exploring even higher dilution rates (up to 10-42), comparing water and brine as solvents for preparing UHDs (4). The studies revealed differences between the T1 and T1/T2 parameters of the UHD when compared with control samples (pure solvents). In particular, the values of the T1/T2 ratios for the studied samples were arranged in the following sequence: water<NaCl solution<UHD of silicon dioxide/lactose (2). With increasing dilution, the T1 value also increased. This was especially pronounced when using brine as a solvent (4). It was thus shown that the presence of a solute increases the degree of structuredness of both water and brine. What is more, this phenomenon also takes place in ultrahigh dilutions of various substances (4). An additional chemical analysis of the samples was later carried out by atomic emission spectroscopy. The UHD's composition revealed an amount of SiO2 larger than expected. It is likely that silicon dioxide is released from the walls of the glass tubes. A high content of this compound was observed even when the initial solution had been diluted to a degree of 1024 times or higher. In line with his findings, Demangeat continued studying UHDs of various substances prepared in plastic dishes.
Subsequently, a study of UHDs of manganese with lactose (diluted from 108 to 1030 times) and histamine (diluted from 108 to 1048 times) (3, 6, 7) found relaxation changes that were similar in nature. It is worth noting that Demangeat was able to distinguish between a UHD of manganese and a UHD of histamine by using discriminant analysis. This may indicate specific organisation of water in these systems (3, 6). Demangeat later also confirmed this result by comparing the PMR relaxation of a histamine UHD to a UHD of arsenic and lactose (8). It is also noteworthy that the identification of UHDs of substances using PMR was only possible with the dynamisation of successive dilutions (8, 10). Thus, the PMR relaxation of water, according to Demangeat, can be a powerful tool for identifying UHDs of substances. Replacing glass tubes with plastic ones, Demangeat obtained similar results (5, 6, 8), which suggests that the SiO2 released from the walls of glass tubes does not affect the observed changes in PMR relaxation.
Demangeat's hypothesis is as follows. During the preparation of UHDs, stable supramolecular structures are formed, including nanobubbles of atmospheric gases and the highly ordered water around them. This is due to intensive mixing between each successive dilution. Solute molecules can act as 'crystallisation centres' (8, 10). This hypothesis is supported by studies conducted by Demangeat into the influence of heating UHDs on their properties (6-8). The previously observed relaxation changes ceased to be recorded after the heating-cooling cycle of UHD samples in sealed tubes. Dr. Demangeat believes that heating contributes to the destruction of nanobubbles and supramolecular structures formed during the production of UHDs. Drawing from the obtained relaxation parameters (based on the analysis of correlations between T1 and T2), the size of the supramolecular structures is estimated at about 4.2 nm for histamine UHDs and somewhat larger for silicon/lactose UHDs (6-8). The article (8) also provides an overview of the properties of nanobubbles in the UHDs. Demangeat suggests that the increase in the degree of organisation of water molecules reflected in the change in PMR relaxation among the solvents used in preparing UHDs occurs in the following order: LiCl solution> NaCl solution> water (5). This is due to the fact that ionic media contribute to the formation and stabilisation of nanobubbles.
In summary, we note the following. In his works, Jean-Louis Demangeat has used PMR to study UHDs of various substances to show that repeated serial dilution with mechanical stirring decreases the mobility of water molecules in the composition of these systems, and therefore increases their degree of organisation. According to Dr. Demangeat, the findings indicate the presence of nanoscale supramolecular structures in UHDs, which are formed 'stereospecifically' around the molecules of the solute, and accumulate upon successive dilution, persisting even above 1024-fold dilution. For all that, Demangeat himself stresses that the PMR method does not allow one to establish the structure of supramolecular formations or to show whether the dissolved substance is retained in the UHD. Through this method, one can 'see' only water. Hence, based on the PMR data, the existence of nanosized particles in the UHD remains a hypothesis.
Dr. Demangeat notes the following unresolved issues: what determines the biological activity of UHDs? Is it the solute or solute-formed nanostructures? Despite the absence of an answer, Demangeat published a review paper in 2018 proposing a possible path and targets for UHD nanoparticles – the olfactory system and olfactory receptors (11). The olfactory system has a direct 'entrance' to the brain and the immune system, and the olfactory receptors are widespread in many tissues. Thus, according to Demangeat, the action of UHDs on the olfactory system can explain their biological effects.
1. New members of our International Editorial Advisory Board. 2001. British Homeopathic Journal. 90 (3): 117.
2. Demangeat JL, Demangeat C, Gries P, Poitevin B, Constantinesco A. (1992). Modifcations des temps de relaxation RMN a 4 MHz des protons du solvant dans les tres hautes dilutions salines de silice/lactose. J Med Nucl Biophys. 16: 135-145.
3. Demangeat JL, Gries P, Poitevin B. (1997). Modification of 4 MHz water proton relaxation times in very high diluted aqueous solutions. In: Bastide M (ed). Signals and Images. Dordrecht: Kluwer Academic Publishers. pp. 95-110.
4. Demangeat JL, Gries P, Poitevin B, Droesbeke JJ, Zahaf T, Maton F, Piérart C, Muller RN. 2004. Low-field NMR water proton longitudinal relaxation in ultrahighly diluted aqueous solutions of silica-lactose prepared in glass material for pharmaceutical use. Appl Magn Reson. 26: 465-481.
5. Demangeat, J.L. (2010). NMR relaxation evidence for solute-induced nanosized superstructures in ultramolecular aqueous dilutions of silica-lactose. Journal of Molecular Liquids, 155 (2-3), pp. 71–79.
6. Demangeat, J.L. (2013). Nanosized solvent superstructures in ultramolecular aqueous dilutions: twenty years’ research using water proton NMR relaxation. Homeopathy, 102 (2), pp. 87-105.
7. Demangeat, J.L. (2009). NMR water proton relaxation in unheated and heated ultrahigh aqueous dilutions of histamine: Evidence for an air-dependent supramolecular organization of water. Journal of Molecular Liquids, 144 (1-2), pp. 32–39.
8. Demangeat, J.L. (2015). Gas nanobubbles and aqueous nanostructures: the crucial role of dynamization. Homeopathy, 104 (2), pp. 101-115.
9. Demangeat JL, Poitevin B. (2001). Nuclear magnetic resonance: let's consolidate the ground before getting excited! Br Homeopath J. 90 (1): 2-4.
10. Demangeat J.L. (2018). Towards a Rational Insight into the Paradox of Homeopathy. Adv Complement Alt Med. 2 (2): pp. 1-13.
11. Courtens, F., Demangeat, J.L., Benabdallah, M. (2018). Could the Olfactory System Be a Target for Homeopathic Remedies as Nanomedicines? The Journal of Alternative and Complementary Medicine.