integral approach to substance abuse and addictionsRead More
A pragmatic randomized controlled trial
, Helmut Friehsemail
, Christiane Thallingeremail
, Narinderjit Kaur Sohalemail
, Christine Marosiemail
, Ilse Muchitschemail
, Katharina Gaertneremail
, Andreas Gleissemail
, Ernst Schusteremail
, Menachem Oberbaumcorrespondenceemailemail
Published Online: March 24, 2015
The use of complementary and alternative medicine has increased over the past decade. The aim of this study was to evaluate whether homeopathy influenced global health status and subjective wellbeing when used as an adjunct to conventional cancer therapy.
In this pragmatic randomized controlled trial, 410 patients, who were treated by standard anti-neoplastic therapy, were randomized to receive or not receive classical homeopathic adjunctive therapy in addition to standard therapy. The study took place at the Medical University Vienna, Department of Medicine I, Clinical Division of Oncology.
Main outcome measures
The main outcome measures were global health status and subjective wellbeing as assessed by the patients. At each of three visits (one baseline, two follow-up visits), patients filled in two different questionnaires.
373 patients yielded at least one of three measurements. The improvement of global health status between visits 1 and 3 was significantly stronger in the homeopathy group by 7.7 (95% CI 2.3–13.0, p = 0.005) when compared with the control group. A significant group difference was also observed with respect to subjective wellbeing by 14.7 (95% CI 8.5–21.0, p < 0.001) in favor of the homeopathic as compared with the control group. Control patients showed a significant improvement only in subjective wellbeing between their first and third visits.
Results suggest that the global health status and subjective wellbeing of cancer patients improve significantly when adjunct classical homeopathic treatment is administered in addition to conventional therapy.
Cancer, Homeopathy, Additive homeopathy, Global health status, Subjective well being
Gelsemium sempervirens effects in vitro: A bridge between homeopathy and molecular biology?
Debora Olioso, Marta Marzotto, Clara Bonafini, Paolo Bellavite
Department of Pathology and Diagnostics, University of Verona
Recent studies conducted in human/animal cells 1-4 have suggested that homeopathic remedies may have an effect on the gene regulation, initiating a cascade of gene actions to correct the disorder or disease at a cellular level. We have focused our attention on the possible
gene modulation effect of Gelsemium sempervirens , a traditional medicinal plant employed in phytotheraphy and homeopathy as a nervous system relaxant to treat various types of anxiety, pain, headache and other ailments. Previous investigations in our laboratory 5 have
shown a significant anxiolytic-like activity of Gelsemium s . high dilutions in mice emotional models. To follow up on the above evidence, we further investigated the Gelsemium s
. mechanism of action in in-vitro neuronal models in order to asses the effects of a wide range of
drug dilutions on whole genome expression 6-7 . For this gene expression study we used sensitive microarray and real-time PCR techniques, able to survey the whole human transcriptome and specific genes of interest respectively. In our case the high-throughput microarray
analysis assisted by bioinformatics could provide a strong clue as to the mechanism of action and the biological relevance of ultra-low doses, whereas the real-time PCR was useful in order to validate the microarray data and to further investigate a narrow group of genes, i.e. a panel
of human neurotransmitter receptors and regulators, involved in neuronal excitatory signaling. To further investigate the possible mechanisms of gene regulation, we also analysed the possible effect of Gelsemium s. on the methylation status of a group of genes involved in mental disorders.
The chief innovation in our experimental design is that it employs a wide range of doses/dilutions: from low dilutions (2c or 3c), where the active substances can still be expected to exert their normal pharmaceutical action, to high dilutions (9c or 30c), where the most controversial
principles of high dilution pharmacology come into play. We think that this type of investigation may be useful to start building a bridge between the more subjective point of view of symptomatology – basis of the homeopathic remedy choice – and a more accurate and objective
one, consisting in the identification of specific molecular markers related with the disease and the prescribed remedy.
Experimental setup Global changes in gene expression produced by exposure to high dilutions of
Gelsemium s . extracts in human neuroblastoma cells were investigated by and real-time
PCR techniques; the methylation analysis was conducted with a PCR Array. Cells were incubated for 24h with the 6 dilutions of Gelsemium s.: 2c, 3c, 4c, 5c, 9c and 30c, produced by
Boiron Laboratoires, according to the French Homeopathic Pharmacopoeia. Four replicate experiments were carried out under identical conditions.
Using microarray analysis, we observed that the diluted drug Gelsemium s . 2c significantly modulates the expression of 56 genes (49 were downregulated and 7 upregulated) involved in neuronal functions (G-protein coupled receptor signalling pathways, calcium
homeostasis, inflammatory response and neuropeptide receptors). The expression of these genes also decreased significantly, although with small changes, after treatment with medium dilution (3c, 4c and 5c) and high dilutions of Gelsemium s 9c and 30c. In the study conducted using the real-time PCR technique (RT-PCR Array) 7 exposure of a human neurocyte cell-line to
Gelsemium s . 2c dilution, containing the active principle gelsemine, induced a down-regulation of most genes of this array. In particular, the treated cells showed a statistically significant down-regulation of the prokineticin receptor 2, whose ligand is a neuropeptide involved in nociception (ability to sense pain), and in depression-like behavior. In the latter study, the 9c dilution was not
active. The difference between the two gene-expression studies 6-7
is probably due to technical factors: while real-time PCR is the “gold standard” for gene expression analysis of specific genes or small groups of genes,
microarray is a powerful screening method for the whole genome and in our conditions exhibited higher sensitivity, detecting extremely low dose effects. In the epigenetic study the Gelsemium s
. 2c treatment induced an increased methylation of the homeobox A1 gene (HOXA1), which has a role in neural development and autism spectrum disorders. The mean methylation frequency after treatment with Gelsemium s . 2c was 53% compared to 28% for the controls (p=0.008).
The increased level of methylation could indicate a reduced gene expression of this autism related gene.
The results of this study, conducted with three different techniques, provided evidence that
Gelsemium s. exerts a prevalently inhibitory effect on a series of genes across a wide dose-range. The results suggest the extreme sensitivity of human gene expression to regulation by
ultra-low doses and high dilutions/dynamizations of a plant remedy and encourage further efforts in research on this field. Studies using sensitive genetic approaches may be particularly suitable for surveing of the effects of highly diluted natural compounds and for the identification of specific molecular markers related with the disease.
Experimental work was supported by grants from Boiron Laboratoires to Verona University – Department of Pathology and Diagnostics and from Italian Research Ministry. The authors have no conflicts of interest.
1. Sunila ES, Kuttan R, Preethi KC, Kuttan G. Dynamized preparations in cell culture.
Evid Based Complement Alternat Med 2009; 6 :257-263.
2. Hofbauer R, Pasching E, Moser D, Frass M. Heparin-binding epidermal growth factor expression in KATO-III cells after Helicobacter pylori stimulation under the influence of strychnos
Nux vomica and Calendula officinalis. Homeopathy 2010; 99 :177-182.
3. Mukherjee A, Boujedaini N, Khuda-Bukhsh AR. Homeopathic Thuja 30C ameliorates benzo(a)pyrene-induced DNA damage, stress and viability of perfused lung cells of mice in vitro.
J Integr Med 2013; 11 :397-404.
4. Sikdar S, Mukherjee A, Ghosh S, Khuda-Bukhsh AR. Condurango glycoside-rich components stimulate DNA damage-induced cell cycle arrest and ROS-mediated caspase-3 dependent apoptosis through inhibition of cell-proliferation in lung cancer, in vitro and in vivo.
Environ Toxicol Pharmacol 2014; 37 :300-314.
5. Magnani P, Conforti A, Zanolin E, Marzotto M, Bellavite P. Dose-effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice. Psychopharmacology
2010; 210(4) :533-45
6. Marzotto M, Olioso D, Brizzi M, Tononi P, Cristofoletti M,
Bellavite P. Extreme sensitivity of gene expression in human
SH-SY5Y neurocytes to ultra-low doses of Gelsemium
BMC Complement Altern Med
7. Olioso D, Marzotto M, Moratti E, Brizzi M, Bellavite P. Effects
of Gelsemium sempervirens L. on pathway-focused gene
expression profiling in neuronal cells.
Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective.
Homeopathy. 2010 Oct;99(4):231-42.
Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective.
Chikramane PS, Suresh AK, Bellare JR, Kane SG.
Department of Chemical Engineering, Indian Institute of Technology, Bombay, Adi Shankaracharya Marg, Powai, Mumbai, Maharashtra, India.
Homeopathy. 2010 Oct;99(4):229-30.
Homeopathy is controversial because medicines in high potencies such as 30c and 200c involve huge dilution factors (10⁶⁰ and 10⁴⁰⁰ respectively) which are many orders of magnitude greater than Avogadro’s number, so that theoretically there should be no measurable remnants of the starting materials. No hypothesis which predicts the retention of properties of starting materials has been proposed nor has any physical entity been shown to exist in these high potency medicines. Using market samples of metal-derived medicines from reputable manufacturers, we have demonstrated for the first time by Transmission Electron Microscopy (TEM), electron diffraction and chemical analysis by Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES), the presence of physical entities in these extreme dilutions, in the form of nanoparticles of the starting metals and their aggregates.
Copyright © 2010 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.