Hormesis
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Biologists often begin their explanation of the biological phenomenon of hormesis by citing the aphorism that what doesn’t kill you makes you stronger. The aphorism implies the existence of agents or activities potentially causing harm, but if insufficient to do so under the circumstances prevailing, actually confer benefit. A simple example: We know that habitually consuming a certain amount 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 of ill health, due to increasing the stores of body fat. Too much of a good thing turns it into a bad thing, so to speak. Thus the in-principle quantifiable biological phenomenon of ‘hormesis’ manifests itself.
In their 2008 New Scientist article entitled, “When a little poison is good for you”, hormetologists Mark Mattson and Edward Calabrese write this of the aphorism:
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It describes the theory of hormesis - a process whereby organisms exposed to low levels of stress or toxins become more resistant to tougher challenges. [1] |
Biologists who specialize in the biochemical and physiological effects of toxic chemicals in living systems — toxicologists — use the term hormesis to refer to the effects of certain (often environmental) chemicals, having definite toxic effects when exposed to the system at certain known doses, yet having beneficial effects when exposed to the system at doses lower than those that cause toxicity. [2] 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.
Hormesis does not manifest itself only in the circumstance of exposure to potentially toxic chemicals, as the example described above relating to gluttony illustrates. Any exposure or activity that tends to stress the living system’s prevailing physiological status can potentially elicit a hormetic biphasic response.[2] "Examples include many chemicals, temperature, radiation, exercise, energy intake and others." [2] 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.
‘Hormetic’ biphasic 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, various stress factors, and certain compounds in plants can also deliver hormetic responses, as can radiation exposure.[1] [2] [3] [4] [5]
References
- ↑ 1.0 1.1 Mattson M, Calabrese E. (2008) When a little poison is good for you. New Scientist 9 August 2008. pp. 34-39.
- From the article: Mark Mattson is chief of the laboratory of Neurosciences at the US National Institute on Aging and a professor of neurosciences at John Hopkins University in Baltimore, Maryland. He is the most highly cited neuroscientist in the world. Edward Calabrese is a professor of toxicology at the University of Massachusetts in Amherst.
- ↑ 2.0 2.1 2.2 2.3 Mattson M. (2008) Hormesis defined. Ageing Res.Rev. 7:1-7. PMID 18162444.
- Abstract: Hormesis is a term used by toxicologists to refer to a biphasic dose-response to an environmental agent characterized by a low dose stimulation or beneficial effect and a high dose inhibitory or toxic effect. In the fields of biology and medicine hormesis is defined as an adaptive response of cells and organisms to a moderate (usually intermittent) stress. Examples include ischemic preconditioning, exercise, dietary energy restriction and exposures to low doses of certain phytochemicals. Recent findings have elucidated the cellular signaling pathways and molecular mechanisms that mediate hormetic responses which typically involve enzymes such as kinases and deacetylases, and transcription factors such as Nrf-2 and NF-kappaB. As a result, cells increase their production of cytoprotective and restorative proteins including growth factors, phase 2 and antioxidant enzymes, and protein chaperones. A better understanding of hormesis mechanisms at the cellular and molecular levels is leading to and to novel approaches for the prevention and treatment of many different diseases.
- ↑ Calabrese EJ, Blain R. (2005) [http://dx.doi.org/10.1016/j.taap.2004.06.023 The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview. Toxicol. Appl. Pharmacol. 202:289-301. PMID 15667834.
- Abstract: A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying a broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings.
- ↑ Calabrese EJ. (2008) Hormesis and medicine. Br. J Clin Pharmacol. PMID 18662293.
- Abstract: Evidence is presented which supports the conclusion that the hormetic dose-response model is the most common and fundamental in the biological and biomedical sciences, being highly generalizable across biological model, endpoint measured and chemical class and physical agent. The paper provides a broad spectrum of applications of the hormesis concept for clinical medicine including anxiety, seizure, memory, stroke, cancer chemotherapy, dermatological processes such as hair growth, osteoporosis, ocular diseases, including retinal detachment, statin effects on cardiovascular function and tumour development, benign prostate enlargement, male sexual behaviours/dysfunctions, and prion diseases.
- ↑ Stumpf WE. (2006) The dose makes the medicine. Drug Discov. Today 11:550-5. PMID 16713907.
- Abstract: Dose and time considerations in the development and use of a drug are important for assessing actions and side effects, as well as predictions of safety and toxicity. This article deals with epistemological aspects of dose selection by probing into the linguistic and cultural roots for the measure of medicine mediated by the medical doctor. Because toxicity is related to dose, historic and recent views suggest that less can be more. At low, medium and high dose levels, effects can differ not only quantitatively but also qualitatively. Dose-related target activation and recognition of enantiodromic thresholds between beneficial and toxic effects require elucidation of underlying events. Such studies, including hormesis and microdosing, call for extended ADME procedures with high-resolution methods in addition to the current low-resolution approaches. Improved information of drug logistics and target pharmacokinetics enables effective drug selection, dose determination and prediction. It also allows considerations of systems biology [i.e. integral (gestalt) pharmacology] exemplified by the drug homunculus, as in the case of vitamin D, that might lead to new paradigms and drug design.