How qualitative and quantitative features of component substances may define the mechanistic pathways of homeopathic remedies.
Much attention has been paid to identification of a single unifying mechanism that underpins the working of homeopathy. This prospect seems unlikely because of the wide range of properties of substances used to prepare homeopathic remedies. As a consequence, it makes sense to consider how different mechanisms may be applicable with respect to the concentration and biological activity of a substance that is used to prepare a remedy. For example, many remedies are prepared from plant extracts and other multi-molecular toxic substances. These are the remedies that best fit the basic principle of homeopathy, “like cures like”.
Other remedies such as silicea prepared from an insoluble substance that contains silicon dioxide, sand, do not contain any or very few molecules (because they are insoluble) and do not have any biological activity. Therefore they must manifest their phenotypic changes by way of a different mechanism compared to the use of homeopathic remedies prepared from biologically active or toxic plant extracts for example.
This commentary outlines some of the alternative mechanisms that may be applicable to understanding more about the workings of homeopathy.
Homeopathic drugs are sometimes administered in a concentrated form, as a Mother Tincture (MT). MTs are the least potent form of a homeopathic drug. MTs often contain substances with measureable pharmacological activity. Therefore, many homeopathic drugs administered as MTs will work in accord with pharmacological/toxicological principles. Their performance will be subject to pharmacogenomic and pharmacogenetic considerations. Therefore ultimately, it may be possible to determine the likely outcome of administration of a MT by pharmacogenetic typing of the drug recipient. (Pharmacogenomics refers broadly to the way in which a drug interacts with and affects the function of a gene or genes. Pharmacogenetics, on the other hand, refers to the way in which a particular gene interacts with a drug to alter the drug’s activity.)
Homeopathic drugs derived from MTs may be further potentised by dilution and succussion, often until pharmacological drug toxicity is largely lost. In these mid-range dilutions, even though pharmacological and toxicological activity may be lost, the small number of remaining substances or molecules may promote biological changes by effecting different types of antagonistic or agonistic cellular responses. These same responses would also be promoted by the administration of MTs, however, it is argued that these antagonistic/agonistic responses would be overwhelmed by the pharmacological properties of the drugs in more concentrated form. (An agonist is a substance or molecule which has the property of binding to a receptor on the surface of a cell resulting in a change in the biological characteristics of that cell.) Importantly, mid-range dilutions of potentised remedies derived from plant extracts have been shown to up-regulate or down-regulate the expression of well over fifty genes, see within Kay and Bukhsh (2016).
On further dilution/potentisation, homeopathic drugs reach a state in which none of the original substance is present. These forms of homeopathic drugs have well documented effects on the biological and psychological phenotypes of an individual. Because such homeopathic drugs have no pharmacologic, agonistic or antagonistic properties, the way/s in which ultra-diluted drugs effect changes to the biological phenotype of an individual have been the subject of great speculation for many years.
Essentially, in the absence of any pharmacological, agonistic or antagonistic activity, changes in the biological or psychological phenotype of an individual must be driven by re-arrangement of the transcriptome. (The term transcriptome refers to the full complement of genes expressed in a particular cell). This means that administration of ultra-high dilutions of homeopathic remedies must in some way have the capacity to re-arrange the transcriptome of various cells in an individual. This possibility was proposed by Khuda-Bukhsh (1997). Since that time, this postulate has been confirmed by numerous homeogenomic in vitro studies, reviewed by Kay and Khuda-Bukhsh (2016).
The finding that homeopathic drugs devoid of the original substance have the capacity to alter the expression of many different genes in vitro is a remarkable discovery. This phenomenon warrants extensive examination. Important work is now required to determine whether these same properties of homeopathic drugs are manifest in vivo.
It is possible to propose a number of ways to explain these remarkable in vitro phenomena, all of which, discussed briefly below, are certainly not mutually exclusive.
Firstly, it is important to consider known mechanisms that are involved in control of expression of a gene. Two well recognised mechanisms that control gene expression involve DNA methylation and the generation of specific interference RNA molecules. (DNA methylation refers to either the addition, or removal, demethylation, of a methyl group, CH3 from DNA. Addition of a methyl group to parts of a gene is associated with reduced gene expression whereas demethylation leads to increased expression of a gene.) With regard to DNA methylation, importantly, Khuda-Bukhsh and Sikdar (2015) have shown that ultra-diluted homeopathic remedies have the capacity to alter the methylation status of various regions of the genome in vitro. Very important work is needed to understand more about the epigenetic properties of ultra-diluted homeopathic remedies, especially with respect to in vivo DNA methylation changes.
With regard to the interference RNA gene controlling system, thus far it is unclear whether ultra-diluted homeopathic remedies can affect this epigenetic machinery. (Interference RNA molecules originate from non-coding regions of the genome. There are a number of different types of interference RNA molecules. Their role is mostly to suppress the activity of a gene.) Investigations are needed to determine whether homeopathic drugs have the capacity to re-direct the interference RNA gene controlling systems.
It is also considered that alteration in the expression of various genes caused by ultra-diluted homeopathic remedies is due to the formation and action of nanoparticles. Malik (2015) has discussed this possibility well. Interestingly, Izquierdo-Lorenzo and colleagues (2010) have demonstrated that metallic nanoparticles have the capability of affecting gene expression by their association with certain agonists. This mode of gene expression re-arrangement may be particularly relevant to the use of metal based homeopathic remedies.
It is also possible that the patient/practitioner contact (part of the case-taking process) also plays an important role in the beneficial re-arrangement of gene expression. This important phenomenon is termed the psychological gene expression system and has been shown by Rossi (2002) to be an integral part of the healing arts. Even though this mechanism may be relevant to homeopathic remediation in some cases, the results of homeogenomic in vitro investigations are incompatible with this prospect. However, the role of the counselling process cannot be excluded as a contributory factor to successful homeopathic remediation.
It is often thought that the benefits of homeopathic remediation may be explicable in terms of a single mechanism. However, due to the vast array of properties of substances that are used to prepare remedies, it is more likely that the benefits or otherwise of homeopathic remedies are due to amalgamation of a range of one or more biological/psychological properties of individual remedy component/s. Importantly, in search of underlying mechanisms, as alluded to above, it is recommended that qualitative and quantitative features of different remedy components are taken into account.
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Izquierdo-Lorenzo I. et al. Adsorption of beta-adrenergic agonists used in sport doping on metal nanoparticles: a detection study based on surface-enhanced Raman scattering. Langmuir. 2010;;26:14663-70. doi: 10.1021/la102590f.
Kay PH, Khuda-Bukhsh AR. The contribution of homeogenetic studies to the support of the practice of homeopathy. Indian Journal of Research in Homeopathy. 2016;10:101-7.
Khuda-Bukhsh AR. Potentized homoeopathic drugs act through regulation of gene-expression: a hypothesis to explain their mechanism and pathways of action in vitro. Complement Ther Med. 1997; 5: 43–46.
Khuda-Bukhsh AR and Sikdar S. Condurango 30C induces epigenetic modification of lung cancer-specific tumour suppressor genes via demethylation. Forsch Komplementmed. 2015; 22 :172-179. doi: 10.1159/000433485.
Malik N. Recent Advances in Nanoparticle Research in Homeopathy. 2015; June.Hpathy Ezine, http://hpathy.com/scientific-research/recent-advances-in-nanoparticle-research-in-homeopathy/
Rossi E. The Psychobiology of Gene Expression: Neuroscience and Neurogenesis in Hypnosis and the Healing Arts. W. W. Norton & Company (29 Aug. 2002) ISBN-10: 0393703436