The Importance of Hormesis to Public Health

Abstract

BackgroundHormesis is a specific type of nonmonotonic dose response whose occurrence has been documented across a broad range of biological models, diverse types of exposure, and a variety of outcomes. The effects that occur at various points along this curve can be interpreted as beneficial or detrimental, depending on the biological or ecologic context in which they occur.ObjectiveBecause hormesis appears to be a relatively common phenomenon that has not yet been incorporated into regulatory practice, the objective of this commentary is to explore some of its more obvious public health and risk assessment implications, with particular reference to issues raised recently within this journal by other authors.DiscussionHormesis appears to be more common than dose–response curves that are currently used in the risk assessment process [e.g., linear no-threshold (LNT)]. Although a number of mechanisms have been identified that explain many hormetic dose–response relationships, better understanding of this phenomenon will likely lead to different strategies not only for the prevention and treatment of disease but also for the promotion of improved public health as it relates to both specific and more holistic health outcomes.ConclusionsWe believe that ignoring hormesis is poor policy because it ignores knowledge that could be used to improve public health.

Conceptual analysis and special-interest science: toxicology and the case of Edward Calabrese

“…(1) Because low-dose effects of some chemicals (like vitamins) have some beneficial effects, and because accepting HD would "not only prevent excess disease or death over background but also promote better health," therefore "public health might be better served by setting exposure standards [HD] at levels using data collected, based on the hormetic model [HG]" (Cook and Calabrese 2006a, p. A688;Cook and Calabrese 2006b, pp. 1632-1634.…”

“…Immunological evidence also shows that combining many low-dose toxins often causes synergistic, not merely additive, effects-as when people are exposed to TCDD and dioxin-like compounds, to radon and smoking, to asbestos and smoking, to alcohol and smoking; additional exposures add to the total, harmful, immunologic and estrogenic burden (Lang 1995). Yet TCDD (dioxin), ionizing radiation, and alcohol are three of the seven main examples that (according to Calabrese) allegedly satisfy H (Cook and Calabrese 2006b;Calabrese 2005;Calabrese and Baldwin 2003b, p. 691). Given these combinations of exposures, as well as multiple exposures, HD thus is irrelevant in a world in which virtually everyone already has had more than low-dose-toxic exposures.…”

“…If none of the hormesis concepts (H, HG, HD) has both regulatory relevance and scientific plausibility, why have Calabrese and others been able to publish their pro-hormesis essays in prestigious journals like Nature and Environmental Health Perspectives (e.g., see Cook and Calabrese 2006b, pp. 1631-1635Calabrese and Baldwin 2003b, p. 691;Calabrese and Baldwin 1999, pp.…”

“…Explanation (3) for the prominence of Calabrese's hormesis articles is that journal referees may have been misled by Calabrese's failure to distinguish different hormesis concepts (H, HG, and HD). By calling all three concepts by the same name, "hormesis" (e.g., Cook and Calabrese 2006b), Calabrese may have confused reviewers. They may have recognized the scientific validity and triviality of one hormesis concept (H), the regulatory relevance of another hormesis concept (HD), then erroneously concluded the same hormesis concept had both scientific validity and regulatory relevance.…”

“…For instance, Cook and Calabrese commit the fallacy of equivocation when, under the heading "FDA Regulation of Hormesis," they claim to be "proponents of hormesis" and urge "regulation of hormesis" (Cook and Calabrese 2006b). They arguably should have said "proponents of HD," and "regulation via HD," because claims positing H are trivially true and irrelevant to regulation, while only invalid claims, positing HG and HD, are relevant to regulation.…”