Hormesis: umbrella mechanism only for agents present in the environment.

Hormesis is a concept of biphasic dose–response to different toxicological and pharmacological stimuli. According to this concept, a noxious agent at a small dose can exert a beneficial action. Among the known hormetic agents are pro-oxidants, heavy metals, heat, radiation, exercise, food restriction and different kinds of stress. All these agents are present in the environment so that the hormetic effect can be explained from the evolutionary viewpoint as living organisms have adapted to a certain level of the impact. For antibiotics, hormetic effects develop secondarily along with the positive selection of resistant microorganisms. Another example is that the adaptation of certain human populations to ethanol for over 1000 years apparently resulted in hormesis; moderate alcohol consumption was reported to be associated with a reduced risk of coronary heart disease and other health benefits. However, the data on hormetic effects of ethanol originated mainly from more developed countries, that is, populations historically adapted to alcohol; and it is questionable whether hormetic effects would be pronounced in people with no historic experience of alcohol consumption. In the author’s opinion, hormesis as a general principle is conceivable only for the factors that are present in the environment, having induced adaptation of living organisms, so that a deviation in either direction from an optimum would be harmful. It is the case, for example, for light or atmospheric pressure, ionizing radiation as well as for many chemical substances and elements. There are no general grounds to expect hormetic dose–responses for factors absent in the natural environment. Discussed explanations for hormetic effects, for example, the homeostasis overshoot hypothesis assuming an excess of repair mechanisms in response to mild damage, or proposed existence of two different receptor types (small numbers of highaffinity receptors and large numbers of low-affinity receptors) appear to be neither sufficiently proven nor universal. Some reported hormetic effects can be questionable because of the difficulties of differentiation complex low-level hormetic responses from the placebo effect, suboptimal design of some studies and so on. Hormesis has been generalized and used, more or less directly, as a theoretic support for homeopathy. Homeopathy claims a curative reaction from a small dose of a drug, of which high doses cause symptoms similar to those from which the patient is suffering. Homeopathy originated in the vacuum of medical knowledge of the 19th century, prior to the acceptance of the germ and gene bases of disease; it was never grounded on empirical scientific evidence. Some publications generalizing hormesis can be cited in support of homeopathy and placebo treatments in gerontology and other fields of medicine, being suitable for endorsement of official registration of drugs and dietary supplements. Suggestions that homeopathy is based on hormesis create an illusion that homeopathy employs a scientific method. There is a well-founded opinion that without supporting evidence for the efficacy or purported mechanisms of homeopathy, the term hormesis should not be linked with it in any way. If homeopaths have useful empirical knowledge, it should be discussed in the professional literature and tested by scientific methods. In some works by Edward Calabrese, the concept of hormesis tends to be treated as a postulate. The question ‘‘Is hormesis likely to occur for all types of