Hormesis and Homeopathy: Toward a New Self-Consciousness
PDF download for Homeopathy: Clarifying its relationship to hormesis, Article Information Bohme H. Hugo Schulz (8/6//31/) His Life and Work. Homeopathy is the best known medical analogue of hormesis, others include Physical and physico-chemical work suggests that homeopathic Adaptation, Physiological/drug effects*; Dose-Response Relationship, Drug*; Drug. Taking into account that both homeopathy and hormesis, as well as their mutual relationships, are attractors of criticism and controversy, this.
In addition, a study found that steroidogenesis is stimulated in Leydig cells by low-dose administration of histamine while inhibited by higher doses. In line with the two-receptor hypothesis, the opposing effects were mediated by subtypes of the same receptor; low-dose administration only allowed for ligand interaction with the stimulatory HRH2 receptor while high-dose administration allowed for ligand interaction with the inhibitory HRH1 receptor. A recent investigation from Zhang et al. However, this investigation did not to investigate the role of other receptors in the observed phenomenon, which does not rule out the possibility that the two-receptor mechanism may be responsible for the given results.
DNA generation DNA damage is a significant mechanism by which toxic substance damage organisms, but it seems that a reversal of this effect may be one of the mechanisms underlying hormesis. Von Zglinicki et al. In addition, mercury is able to stimulate synthesis of metallothionein, which can clear toxic metals from the body, thereby protecting cells from free radical damage generated by normal metabolism.
Under normal circumstances, the generation and removal of ROS in the body are tightly regulated, which allow them to serve beneficial roles while avoiding their deleterious effects. However, if ROS cannot be removed quickly, they will accumulate, which can be damaging to the body. Thus, moderate levels of ROS seem to exert a stimulatory effect on the body.
However, it is well-known that high levels of ROS stimulate apoptosis or necrosis in all cells. Thus, it seems that hormetic effects can be mediated by mechanisms other than the two-receptor hypothesis. Enhancement of immune function Arinaga et al. Moreover, animal experimental data show that low-dose stimulation may enhance the body's immune function by: Gene expression and regulation Research shows that hormesis is closely related to expression and regulation of genes involved in DNA repair, stress protein production, growth, transcription factors, transcriptional promoters, and apoptosis.
One class of hormesis research is only concerned with the quantitative characterization of hormetic stimulation and its parameters, including the width and breadth of the stimulatory range as shown in [Figure 1]. Over the past few decades, scholars have put forth a variety of dose-response models to characterize the hormesis phenomenon, including the biphasic dose-response model  [Equation 1] and Brain-Cousens model  [Equation 2].
In the field of mixed hormesis quantitative study, researchers have put forth the corresponding hybrid hormesis quantitative method based on the quantitative study of single-compound hormesis and supplemented by traditional quantitative methods for determining toxicity for interactive mixtures. For example, Ge et al. Hormesis of ionic liquid mixture on the luminescent bacteria Click here to view As an alternative, a novel model, the "six-point" model was proposed for predicting the hormetic effects of mixtures in low dose.
The six-point model was developed based on the quantitative structure-activity relationship approach and the quantitative features in the determined dose-response curve. The results indicated that this model can accurately predict the hormetic effects of mixtures in low dose not only for noninteractive mixtures but also for interactive mixtures as well. Therefore, the "six-point" model is a powerful tool to predict the hormetic effects of mixtures at low doses and may serve as a more accurate tool for assessing the environmental risk of toxin mixtures.
Despite these recent advances, current research on hormesis for both single and combined quantitative characterization parameters according to the dose-response curve for external characteristics lacks an understanding of chemical toxicity mechanisms and fails to provide support to its specific biological significance.
Thus, it is necessary to investigate these areas of ambiguity if we hope to accurately assess the risk of toxin exposure. Applications 0Hormesis will significantly influence the current risk assessment process Two basic models are generally used in toxicology: Threshold model and linear nonthreshold model. The former is used to assess the risk of noncarcinogens and the latter is extrapolated for the risk of carcinogenic substances at very low concentrations.
Compared with these two traditional models, hormesis is better able to predict the toxic behavior of compounds at low dose.
- Update on hormesis and its relation to homeopathy.
- Hormesis and homeopathy: The artificial twins
- Hormesis and Homeopathy: Toward a New Self-Consciousness
This default dose-response model would be used for risk assessments in the absence of convincing reason to employ a different model. Specifically, in biological experiments and human epidemiological investigations, we should simulate and analyze dose-effect relationships according to the specific characteristics of a given compound and dose, rather than simply extending a linear extrapolation of the traditional risk assessment.
In addition, during experimental design, low-concentration groups should be included, as well as a more extensive dose range to investigate the effect of hormesis. Furthermore, the authors reveal that the biological responses induced by these homeopathic remedies show the traits that would normally characterize a hormetic dose—response mechanism.
In this context, there are a few more points I want to mention here that deserve particular consideration. Two important sets of experiments have been reported in the last few years. The first concerns the above-mentioned studies by the Bellare group using electron diffraction and electron transmission microscopy techniques. According to the authors, this is due to the formation of an enriched monolayer of nanoparticles on the surface due to froth flotation induced by succussion, that is, a particular vigorous shaking procedure.
This monolayer is maintained in the dilution process. Two points are worth mentioning here: The succussion procedure itself means that all the diluted and succussed solutions contain metasilicate oligomers due to the glass containers. Studies reported by several research groups show that homeopathic medicines of different concentrations affect the gene expression profiles of different DNA microarrays when compared with controls.
In other words, the action of drugs is not suppressed by ultrahigh dilution and proceeds through the modulation of gene expression, thus indicating that their efficacy is maintained. This result would seem to have 2 consequences: These results would therefore support the efficacy of homeopathy due to certain mysterious mechanisms.
Hypotheses like water memory, 33 — 35 quantum mechanical effects like bio-phonons and resonance coherent domains, 36 — 39 or clathrate formation 40 have been proposed and obviously strongly criticized by the scientific community. However, it is important to stress another important point which could be considered crucial to clarifying the problem: All the above-mentioned research used a single dilution of the homeopathic preparation.
Studies carried out by 2 independent groups 42 — 47 show that by treating the DNA microarrays with homeopathic remedies Gelsemium sempervirens and Apis mellifica in different concentrations, including 15 CH and 30 CH, the response of the biological system decreases with increased dilution of the homeopathic medicine. It is hard to understand and to accept that the water memory and the others of the above-mentioned physical proposals should be affected by serial dilution.
Therefore, it seems reasonable to suggest that the latter results are consistent with a drug concentration which is different from that expected.
The conclusion is different from the Bellare group, 3 — 5 which suggests a constant number of metal nanoparticles below a certain metal concentration, despite the serial dilution. The formation of molecular nano-associates in aqueous solutions, which were prepared using serial dilution, has recently been reported and discussed. Since homeopathic remedies are prepared by diluting and succussing a concentrated solution, it can be expected that the number of molecules which populate the interface is small compared to those in the bulk.
Therefore, in practice, we observe first the canonical linear dilution behavior and then a less enhanced dilution effect due to the preferential solute—solute interactions at the interface. It is obvious that the peculiar nature of the layer depends on the details of the species, and this may explain the difference between metal nanoparticles and organic molecules. In addition, for Gelsemium sempervirens and Apis mellifica, this fact may play a role since the natural remedy is made up of many different components.
However, if the above arguments hold, it can be argued that the majority of homeopathic remedies are always at non-zero concentration, against any formal expectation.
This is difficult to demonstrate using the same physical techniques employed by the Bellare group, due to the different nature of the substances investigated metal nanoparticles vs organic moleculesbut it seems to offer a rationale to the observed pattern of reactivity toward DNA microarrays. If this statement holds, homeopathy should not be considered a nebulous therapeutic approach, where, as is believed and claimed at present, unclear mechanisms of information transfer operate to shift a living organism from a pathological attractor toward a normal physiological one.
This is covered in the article that I had written with Belke and Oldman. In contrast, Calabrese and Baldwin, in their Nature commentary, go on to propose that the public has been unnecessarily frightened by assumptions underlying risk-assessment. And instead of protecting against low doses, in fact, this fear should be replaced by the recognition that low doses are beneficial.
Hormesis is a description of a particular type of dose-response relationship. Hormetic dose-response curves are, in fact, common for endocrine disruptors.
The Debate Over Low Doses: Hormesis & Human Health
Basically, the premise by regulators is that as dose moves from a very high level down to a threshold, below that threshold, you can reach a safe exposure level. The dose-response curve is always assumed to be monotonic. None of these receptor-mediated responses are currently part of the existing paradigms for looking at effects that are only examined at very high doses.
So this whole approach contrasts with what is proposed by Calabrese -- that acceptance by the EPA of hormetic curves would lead to acceptance of a threshold model. We respond that, in fact, it should lead to rejection of the threshold model, because the system under attack by these environmental estrogens is already above threshold induced by endogenous estrogens.
Dan Sheehan in EHP has a wonderful article on this. Myriam Laura Beaulne, who is on the call, has been helping to coordinate that for us. Another issue is that this certainly has not been shown to be a generalizable hypothesis. If you look at the databases upon which Calabrese and colleagues argue that hormesis is generalizable, most of these cases are plants and lower mammals. That leads to a number of reasons why it would be very irresponsible to integrate hormesis into regulatory policy.
I started from a sort of fundamental, principal public health, which is protecting those most vulnerable in a population. The first is human variability.
We know that certainly there might be a hormetic effect in a single individual. But are there other individuals in the population that might have a negative effect from that same dose? But we must consider those with compromised immune systems, or those with lower socioeconomic status. We have a background of substances. And many substances cause toxic effect through similar modes of action.
So we have the issue of interaction.
Does homeopathy have anything to contribute to hormesis?
Next point is that the database on which hormesis is based is based on single endpoints. We know that a single toxic chemical at a single dose can cause multiple endpoint damage.
So while one effect might show a hormetic positive response, another effect might show a negative response. Also, stimulation may just be an indicator or a precursor of an adverse effect.
There are the costs of delay of chasing hormesis -- our cost to health. Not cost to industry. So, in the end, if we were to accept hormesis as a part of the regulatory paradigm, we should be treating those chemicals that are argued to have hormetic effects, like drugs. We should be conducting clinical trials. There should be dose control, and there should be, obviously, informed consent. So there are a series of requirements before we could ever accept, responsibly, hormesis in the regulatory paradigm.
There would have to be no variability. You would have to have controlled-exposures. You would have to have controlled background. You would have to demonstrate that there is a beneficial effect. So in the end, hormesis is a very interesting academic exercise, as Fred was explaining. The problem is really the low-dose harmful effects of chemicals. Finally, do we need to worry? We need to be cognizant of this happening, and respond. But remember that the vast majority of the literature on hormesis is from a single person.
The database is weak. So we need to respond, but not worry too much, at this point, I think. We need to be clear that this is a problem, and we need to respond to it. Joel, thank you very, very much.
I just want to re-emphasize the efforts we made to encourage Dr. Calabrese to be on the call. Because truly, our goal is to raise the level of public and professional dialogue about how the environment affects human health. I want to start with some of the scientists on the call.
Does homeopathy have anything to contribute to hormesis?
I think his argument is very strong, and something we should take it into consideration. Hormesis is too vague. As he said, it would be almost impossible to incorporate it into any kind of risk-analysis or risk policy. I hope Joel is right. A lot of examples of potentially positive effects have been brought in the work that Dr. Calabrese has published, but I think we need to have a more subjective view. And I invite Fred, if he could take us through the numbers of studies that have demonstrated harmful effects of very low doses.
None of them could be considered as anything but adverse. Then, as you move to ,fold higher dose, these effects go away. And if you started from high doses and moved down from very high doses, you would not see them. As I say, there are 11 major papers published, showing these kinds of dose-response curves. So certainly we know there are low-dose impacts of chemicals. We know that the U-shaped or bi-phasic dose response is common, in some cases.
The response I would say is that we have to come up with a strategy that promotes the idea that risk-assessment has to accept that there are dose-response curves other than monotonic functions, that essentially discredit the linear threshold model of risk-assessment for non-carcinogenic chemicals.