The Dose-Response Revolution: How Hormesis Became Significant: An Historical and Personal Reflection

“Hormesis” is defined in toxicology as the “biphasic dose response to any environmental agent — characterized by a low-dose stimulation, or beneficial effect, and then a high-dose inhibitory, or toxic, effect.” In the research areas of biology and medicine, “hormesis” is defined as an “adaptive response of cells and organisms to a moderate (usually intermittent) stress.” Hence, this topic falls within gene-environment interactions and has been previously discussed many times in these GEITP pages.

Author Calabrese [see first attachment; which is Chapter 1 of a book to appear later this month] tells the story of how hormesis emerged from a marginalized dose-response concept — that had been significantly weakened by its historical association with homeopathy — to become widely recognized as a central concept in evolution, biology, toxicology, and medicine. The chapter is set within the framework of personal reflections by the author, concerning key aspects of how this dose-response revolution occurred and the nature of its biological and biomedical significance.

During the 1980s decade, the number of citations (of terms ‘hormesis’ or ‘hormetic’) was ~10 per year. By the year 2000, there were ~400 citations for ‘hormesis’ or ‘hormetic’; and, in 2017, the number had jumped to more than 9,200. The areas of hormetic research are very broad, cutting across a wide range of disciplines and topics. Many topics gain attention for a few years, and then recede, due to the fact that they were discredited or oversold. In the case of hormesis, it has always been underestimated.

A major reason for the strong and sustained growth of hormesis is principally because hormesis is at the core of the adaptive response. The biomedical sciences started to appreciate hormesis about a decade ago and realized that medicine and public health successes can be driven and mediated by the up-regulation of adaptive mechanisms. Protective mechanisms in the cell or organism can be effective in healthy aging and be similarly useful in protecting people from a vast array of life-threatening conditions such as heart attack, stroke, traumatic injury to the brain,, numerous neurodegenerative diseases, diabetes, and other debilitating diseases.

For those interested, the second attachment summarizes the Oct 3 2o18 testimony of Calabrese before the Senate “Environment and Public Works Subcommittee on Superfund, Waste Management and Regulatory Oversight.” The presentation specifically addresses the “Oversight of the Environmental Protection Agency’s (EPA’s) Implementation of Sound and Transparent Science in Regulation” — in order to establish the best, safest, and most rational public policies.


The Science of Hormesis in Health and Longevity, (Suresh I, Rattan S, Kyriazi M, eds.), 1st Edition, published 26 October 2018

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