Hormesis

Note: Text in font-color Blue link to articles in Citizendium; text in font-color Maroon link to articles not yet started; authors/editors encouraged to initiate articles not yet started. Text in italic font-color dark-blue indicate a direct quote. Text in bold font-color Dark Brown used for special emphasis.

---

Hormesis is a technical term used in toxicology to refer to a quantitative and qualitative dose-response, or concentration-effect, relationship in which the effect at low concentrations occurs in the opposite direction from that expected from the effect observed at higher concentrations. For example, a toxin that inhibits function of a biological component in certain known doses stimulates the function of that component at lower doses. Interest seems to concentrate on instances in which the low-dose effect confers benefit whereas the high-dose effect exhibits detriment. Some biologists, including health science biologists, often use 'hormesis' to refer to an adaptive response of cells and organisms to various categories of 'stress', an adaptation characterized by resistance to the stressor when previously exposed to it at low levels,

Biologists often begin their description of the biological phenomenon of hormesis by citing the aphorism that what doesn’t kill you makes you stronger, or the aphorism that what makes something a medicine or a poison depends on dose. The first aphorism implies the existence of agents or events potentially causing harm, but if insufficient to do so under the circumstances prevailing, actually confer benefit. A simple example: We know that habitually consuming certain amounts of food increases our chances for a long healthy life — a beneficial effect — but that habitually consuming food in certain larger amounts, all other things equal, can result in numerous deleterious physiological/biochemical manifestations, some at least due to excessively-increasing the stores of body fat. Some bad things, so to speak, arise from too much of good things. The example of the first aphorism applies also to the second aphorism. Thus the quantifiable in-principle biological phenomenon of ‘hormesis’ manifests itself.

In their 2008 New Scientist article entitled, "Best in Small Doses", hormesiologists Mark Mattson and Edward Calabrese write this applicable to the aphorism about adaptation:

It describes the theory of hormesis - a process whereby organisms exposed to low levels of stress or toxins become more resistant to tougher challenges.

[New Scientist editors announce the article as "When a little poison is good for you".]

Biologists who specialize in the biochemical and physiological effects of toxic chemicals in living systems — toxicologists — use 'hormesis' to refer to the effects of certain (often environmental) chemicals, having definite toxic effects when exposed to the system above certain known doses, yet having beneficial effects when exposed to the system at doses lower than those that cause toxicity. They refer to the effect as “biphasic”: beneficial at 'low' doses, toxic at 'high' doses. 'Beneficial' may mean only that the agent stimulates a biochemical or physiological phenomenon at low doses and inhibits it at high doses, and does not necessarily mean beneficial in the strict positive sense of the word.

Hormesis manifests itself not only in the circumstance of exposure to potentially toxic chemicals, as the example described above relating to gluttony illustrates. Any exposure or event that tends to stress the living system’s prevailing physiological status can potentially elicit a hormetic biphasic response. "Examples include many chemicals, temperature, radiation, exercise, energy intake and others." Increasing the amount of physical activity by a more-or-less sedentary person, while it constitutes a stress on the cardiovascular and neuromuscular system long accustomed to relatively modest demands, may benefit the person’s general state of health. But an overenthusiastic convert to exercise may perform too much too quickly, resulting in injuries of many different kinds.

Mattson and Calabrese add another twist to hormesis, defining it as "a process whereby organisms exposed to low levels of stress or toxin become more resistant to tougher challenges" [emphasis added (as underline)] They write of the manifold defense molecules that the body actuates when a threat appears, that calling them to duty, so to speak, both counters the actuating threat and increases the body's ability to resist other threats. They exemplify that with the nerve cell toxicity produced by the high levels of the neurotransmitter, glutamate, that brain injury may release into the synapses connecting nerve cells, but which at lower levels can beneficially affect nerve cell survival and growth. As another example of what they call "hormetic stressors", they write of the natural plant chemicals that act as 'natural' pesticides, protecting the plants against 'natural' pests. In the amounts of those so-called phytochemicals that we consume with our fruit and vegetables, they actuate our body's responses to stress, but in high enough doses can cause toxic injury.

‘Hormetic’ dose-response effects occur commonly and appear as a general biological phenomenon among numerous animal species, non-gender- or age-specific, among microorganisms as well. The response parameters — the effects displaying hormetic biphasicity — include growth, longevity, metabolic phenomena, disease incidence, cognitive functions, and immune responses. Exercise, caloric restriction, ethanol, caffeine, and various other stress factors, including radiation exposure, can also deliver hormetic responses.  

British hormesiologist A. R. D. Stebbing explains the hormetic effect as an evolved biological adaptation that prepares organisms to resist the toxic effects of a range of different environmental stressors, comparable to the evolved biological adaptation referred to as 'homeostasis':

Ockam’s Razor leads one to look for the most economical hypothesis, which for hormesis is more likely to depend on some common property of the organisms than the toxic agents to which they are exposed. The range of examples suggests that hormesis is not so much an effect of the specific agents that induce it, but an adaptive response to the inhibitory effect they share, because it is improbable that any toxicant-specific interpretation could account for the widespread occurrence of the b[eta]-curve [the biphasic hormetic curve]. The idea that hormesis is due to a biological response is also attractive in an evolutionary sense, because organisms are thus pre-adapted to toxic inhibition whatever the specific cause.

At low doses of stressor, the evolved adaptive, or homeostatic, mechanism 'overcompensates', bringing about the stimulatory or beneficial effect, the 'overcompensation' feature itself an evolved adaptive mechanism that strengthens with exposure to the stressor, accounting for ....a process whereby organisms exposed to low levels of stress or toxins become more resistant to tougher challenges. 

Scientists have not universally accepted hormesis, though the discussion remains active.

History of hormesis

Hormesiologist A.R.D. Stebbing offers a succinct account of the history of the phenomenon and concept of hormesis:

Examples of hormesis gathered from the literature show that hormesis has a long and interesting history. The concentration-response curves for quite a wide range of toxic agents followed a typical pattern, termed the betacurve (Townsend & Luckey, 1960). The occurrence of such curves in toxicological experiments was discovered independently and named on several occasions. Over a century ago Schultz's experiments (1888) showed that many chemical agents had the effect of stimulating the growth and respiration of yeast. The phenomenon became known as the Arndt-Schultz Law and was widely referred to in the pharmacological literature for over 30 years and became one of the scientific principles on which homeopathy is based. However, the potency of homeopathic medicines is believed to increase with their dilution over many orders of magnitude, rather than restricted to a narrow range of concentrations like hormesis.  Hueppe (1896) at about that time made similar observations on bacteria, apparently unaware of Schultz's experiments. His generalization became known as Hueppe's Rule.  Long before them both, the German alchemist and physician Theophrastus Bombastus von Hohenheim ((1493-1541), who coined for himself the name *Paracelsus*, had recognized with respect to the medical use of small amounts of toxic chemicals that their efficacy depended principally on the dose. Such ideas are perhaps more easily accepted nowadays, when it is in the experience of most to use the stimulatory effects of alcohol, caffeine or nicotine, all of which are toxic at high concentrations.  Much later Southam and Ehrlich (1943) studied the effect of a natural antibiotic in cedar wood that inhibits the growth of wood-decaying fungi. They found that subinhibitory concentrations of the antibiotic had the reverse effect and stimulated fungal growth. The term "hormesis" was coined to describe it; which we still use today. Some of the observations have an interesting origin. In the later stages of World War II, when supplies of penicillin were in such short supply, work of Miller et al. (1945) explained why reducing the dose to make short supplies of the new drug go further sometimes had the reverse of the desired effect. At low doses penicillin actually stimulated the growth of Staphylococcus . In other examples closer to my own field, experiments with oyster lar vae showed that low levels of many pesticides actually stimulated growth in the same way (Davis & Hidu, 1969). The greatest authority in the field of hormesis is Dr Thomas Luckey, whose early work was on the use of antibiotics as dietary supplements to stimulate growth in poultry (Luckey, 1956).   [Note: References cited by Professor Stebbing in this excerpt: ] References and notes cited in text Many citations to articles listed here include links to full-text — in font-color blue. Accessing full-text may require personal or institutional subscription to the source. Nevertheless, many do offer free full-text, and if not, usually offer text or links that show the abstracts of the articles. Links to books variously may open to full-text, or to the publishers' description of the book with or without downloadable selected chapters, reviews, and table of contents. Books with links to Google Books often offer extensive previews of the books' text.