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Homeopathy 2026; 115(01): 048-050
DOI: 10.1055/a-2633-6321
Letter to the Editor

Response to the Letter to the Editor: Ultradiluted Homeopathic Medicines Cause Apoptosis in RPMI-8226 Multiple Myeloma Cells: a Critical Appraisal

Authors

  • Buket Altinok Gunes 

    1   Vocational School of Health Services, Ankara University, Ankara, Turkey
    2   Department of Medical Biology, Faculty of Medicine, Ankara University, Ankara, Turkey

  • Murat Kilic 

    1   Vocational School of Health Services, Ankara University, Ankara, Turkey

  • Tulin Ozkan 

    2   Department of Medical Biology, Faculty of Medicine, Ankara University, Ankara, Turkey

  • Nurbanu Gonulkirmaz 

    2   Department of Medical Biology, Faculty of Medicine, Ankara University, Ankara, Turkey

  • Nurcihan Guven 

    3   Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey

  • Asuman Sunguroglu 

    2   Department of Medical Biology, Faculty of Medicine, Ankara University, Ankara, Turkey
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Ultradiluted Homeopathic Medicines Cause Apoptosis in RPMI-8226 Multiple Myeloma Cells: A Critical AppraisalHomeopathy 2026; 115(01): 046-047
DOI: 10.1055/a-2606-5872

Ultradiluted Homeopathic Medicines Cause Apoptosis in RPMI-8226 Multiple Myeloma Cells: A Critical Appraisal

We thank Dr Shekhar and colleagues for their letter entitled, “Ultradiluted homeopathic medicines cause apoptosis in RPMI-8226 multiple myeloma cells in vitro: a critical appraisal”, published in Homeopathy.[1] Such constructive criticism in the scientific field, especially in controversial or new areas of research, forms the basis of scientific progress. We address here the main points highlighted in the letter.

Physicochemical Analysis of Ultradiluted Preparations

Homeopathic medicines with their various dilutions are prepared by experts such as homeopathic pharmacists. They are being utilized as an alternative or complementary mode of treatment in many countries in the world. Naturally, we agree with Shekhar et al that every homeopathic remedy should ideally be examined extensively during the manufacturing phase using high-resolution microscopic techniques, UV spectroscopy, or nanoparticle tracking analysis. We accept the criticism of our original study[2] regarding the absence of physicochemical characterization at high levels of dilution as valid and critical in this context. However, we would like to re-emphasize that ours was a pilot study intended to determine whether there are measurable biological effects in multiple myeloma (MM) cells from any of four 200C-potency remedies in a standard laboratory setting using our own equipment. Our goal was to investigate the biological response, not the molecule. However, we want to stress that, as explained and the results discussed below, our study is methodologically identical to cell-based research conducted at similarly high concentrations by researchers such as Frenkel and Sikdar.[3] [4]

The existence of starting material nanoparticles in ultradilute homeopathic preparations can rightly be questioned. This concern has already been addressed by one other goal of our work—will there be cytotoxicity or apoptosis despite this much dilution? Our reproducible detection of highly diluted remedies' bioactivity is highlighted by the facts that the experimental sets were repeated three times each, that some of the experiments were re-done as a consequence of editorial requests made in the course of article review, and that we consistently observed cytotoxic, apoptotic and even cell cycle arrest effects on the cell line in question.

There is an increasing amount of evidence suggesting that homeopathic preparations, including highly diluted liquids, contain nanoparticles of the original material. However, it is unclear whether the globules contain such potent nanoparticles. For instance, in 2010 and 2017 Chikramane et al[5] [6] showed that high potency (30C and 200C) metal-based homeopathics contain nanoparticles. Despite high rates of dilution, Temgire et al reported that these nanoparticles were present in a hydrogenated and surface-enriched form.[7] The occurrence of nanoparticles in homeopathic solutions has also been the subject of study by Gonçalves et al: these results challenge the idea that homeopathic medicines are merely water and suggest that they may have nanomedicinal effects.[8] In 2012, Patel et al reported that 200cH metal salts comprise nanoparticles, highlighting the need for additional chemical analysis and equipment.[9]


Preparing Drugs and Excipient Residues

As per clinical practice, our medication in the form of drugs was prepared by dissolving medicated starch globules in sterile distilled water. Centrifugation removed fresh particle starches prepared for each trial, and controls were prepared from the same distilled water. There was less systematic bias in all groups by this procedure. But in our subsequent work, we shall only have solvent (succussed vehicle) control groups to give a tighter experimental control.

It is an excellent criticism by Shekhar et al[1] that the word “blind” is never actually mentioned under the Methods section of our paper. We do want to clarify, however, that technical staff were not aware of the sample identities while performing all MTT, flow cytometry, and propidium iodide staining experiments. Furthermore, as is properly the case for all researchers in all studies, we work blindedly. We know that this is an ethical necessity. In the name of transparency and consistency in method, we will elucidate this aspect—which we did not address in particular in the article—more clearly in our future studies.


Making Use of Just One Cell Line

In the Introduction section of our article, we tried to explain the (complementary) role of homeopathy in cancer treatment, citing the research of scientists who have taken an in vitro and an in vivo biological approach to its experimental investigation. From this viewpoint, our aim was to compare the biological effects of four distinct treatments on MM cell lines, which we screened in accordance with the equipment available in our laboratory. In our study, we consciously avoided making the overall generalization that homeopathy is an effective treatment for all cancers. We referenced our findings according to the MM cell line as a point of reference. Therefore, to remain true to our mission, we selected a cancer cell line that had never been investigated by any study in the literature, while constrained within a minimal budget. This decision was made in light of our aim to evaluate the effect of homeopathic medicines on MM cells for the first time at an in vitro level, as well as to carry out an extensive characterization of the cell line involved.


Absence of Mechanistic Results (Gene Expression, Caspase Activation, etc.)

The investigation of molecular studies on the apoptosis pathway, such as caspase activation and PARP cleavage, as well as the determination of gene expression profiles, would definitely increase the biological validity of the findings. However, as emphasized in the critique of our work, the objective of this pilot study—highlighted as significant in terms of its contribution to the literature—was solely to present preliminary data on the effects of homeopathic preparations on apoptosis and the cell cycle.


Justification for Selecting 200C Potency

The 200C potency was chosen on the basis of some preliminary experiments in the literature. Specifically, in Arora et al's (2013) in vitro study, mother tincture (MT), 30C, 200C, 1M and 10M potencies of homeopathic remedies such as Sarsaparilla, Ruta graveolens and Phytolacca decandra were assessed for dose-dependent cytotoxic activity against various cancer cell lines (kidney, colon and breast). Elevated dilutions, such as 200C potency, demonstrated substantial anti-proliferative activity here, although MT exerted the most effect. This circumstance renders plausible the likelihood of biological activity at high potencies, which these scientists underscored.[10] On this basis, the 200C potency was chosen for our study because initial findings in the literature exist that high potencies may be cytotoxic, and also because it is commonly chosen in the clinical setting.


Variability in Cell Cycle Results

That only Hecla lava and Carboneum sulphuratum caused significant cell cycle arrest in the sub-G0/G1 phase might indicate preparation-specific pharmacodynamic differences. Although this method might represent a scientific inconsistency, we believe that it suggests that each preparation might have differing mechanisms of action. In this context, it is noteworthy that the effects of Carboneum sulphuratum have been demonstrated in the literature for the first time by our work.[2]


Future Perspective and Clinical Interpretation

As stated in the letter to the editor,[1] we agree that caution should be exercised when translating the findings to clinical practice. Clinical effectiveness is not a claim of our research. However, these results provide a strong basis for new, large-scale studies targeting molecular mechanisms to evaluate the potential complementary effects of homeopathic remedies against a difficult cancer type such as MM.


Conclusion

We reiterate our thanks to the authors of the letter[1] for their constructive criticism of our work. Such scientific discussions are important for a deeper understanding of the subject and for producing science based on the most solid evidence. While acknowledging the limitations of our pilot research, we would emphasize that as we secure financial support for the study costs, we will continue to work on multi-center, blinded experimental designs involving different cell lines to expand and validate our findings.




Publication History

Received: 04 June 2025

Accepted: 11 June 2025

Article published online:
28 August 2025

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