Homeopathy and Nanomedicine: Alien Twins
13 May 2019
19 May 2019
01 August 2019 (online)
In his recently published article, Dr. Rajendran has claimed that homeopathy is a kind of nanomedicine, citing a number of articles reporting the presence of nanoscale particles in homeopathic medicines (HMs). However, some of the above-proposed reasons and evidence are questionable regarding the “nanoscience” criterion. As pharmaceutical nanotechnologists, we wish to point out some of the more debatable points presented in the cited evidence that supports the nanoparticle (NP) hypothesis for homeopathy.
Considering the NP content, HMs are very heterogeneous in nature. A significant poly-dispersity from the amount of the starting material to the size and shape of NPs is obvious. While some studies showed different amounts of the starting material in the placebo control (solvent), some HMs had no trace of the starting material [Rajendran's refs. 5-6].[a] Chikramane et al have reported a “considerable batch-to-batch variation in the concentrations of the starting material”. If HMs work based on NPs, then a non-reproducible therapeutic outcome would be expected due to such high inter- and intra-batch variations. NPs were found in different shapes and a wide range of sizes from a few nanometers to micrometers [refs. 5, 9, 15–19]. The size of some found particles, which are claimed to be NP aggregates, is rarely in the nanoscale. It is well known that the properties of NPs, and consequently their biological effects, are size- and shape-dependent. Heterogeneity in size and shape would inevitably lead to heterogeneity and non-reproducibility in biological outcomes of NP therapeutics. That is why content uniformity is of utmost importance in nanomedicine.
Microscopy images, including transmission electron microscopy, scanning electron microscopy, and atomic force microscopy, are potentially very misleading and are highly dependent on interpretation: that is, no definitive judgment can be made on such images alone. Decreasing volume of a droplet due to solvent evaporation can cause self-organization and crystallization of the solutes. Thus, it is quite conceivable that some of the presented microscopy images are showing such sediments rather than colloidal NPs. At least one ensemble method (e.g., dynamic light scattering [DLS] or nanoparticle tracking analysis [NTA]) is essential, alongside microscopy, for characterization of NPs. Similarly, DLS alone is not conclusive for size determination where NPs are heterogeneous in size and shape. In addition, since NTA cannot discriminate between nanobubbles and real NPs, it may overestimate the number of NPs and is not a determinant method by itself. These methods can provide more reliable results when used together.
Looking for NPs in a medium needs a clean room environment: otherwise, nano-sized air pollutants or airborne NPs may contaminate the sample. Upadhyay, in his recent article, has asserted that what Chikramane et al found “are nothing but contaminant”. It is therefore recommended that the HMs be prepared (as they are already prepared in some laboratories) and examined in clean rooms to avoid any contamination during and after preparation. The purity of the solvent and the cleanliness of the containers should also be considered.
Moreover, as pointed out by others, there seems to be a relative lack of “adequate” controls—for example, pure solvent, potentized solvent, or equal dilution of starting material without succussion—to determine that these observations are unique to homeopathically prepared solutions. The importance of this point becomes much clearer when control samples are shown to contain NPs, even more than some HM samples [refs. 6-7, 9]. A recent study performed by Van Wassenhoven et al, using good pharmaceutical practice and proper controls, did not reproduce and confirm the results obtained by Chikramane et al. They also could not find a significant difference “between a simple dilution and a homeopathic potency”.
The mere presence of NPs in HMs is not sufficient to equate homeopathy with nanomedicine. Finding “something” where homeopathy's critics believe there is “nothing” is intriguing, but that can only provide evidence for the content of ultra-dilutions and does not necessarily mean that any such NPs would be responsible for the pharmacologic activity of the HMs. We would need proof that NPs are directly produced by homeopathic preparation techniques and, further, that such NPs are essential for a specific therapeutic effect and are not just contaminants or by-products of the HM preparation procedure. It would be worthwhile testing whether the therapeutic effects of HMs are retained after removal of the particles present—for example, by ultra-filtration or ultra-centrifugation—and then to test whether the same concentrations of identical NPs, prepared by methods different from those used for HMs, have the same therapeutic outcomes. At least one study, which compared the biological effects of homeopathic arsenic (Arsenicum album) before and after removal of particles by centrifugation, showed no correlation between the presence of particles and biological effects.
We have no position against the proposed nanoparticulate hypothesis for homeopathy, but wish to highlight the inadequacy of evidence, given that current findings are inconsistent and insufficient. Additional and more carefully designed experiments are required.
# Joint first authors
Both the authors contributed equally to this article.
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