*Geek Box: Hormesis
‘Hormesis’ is a principle from toxicology, and describes how exposure of an organism to a physical or chemical agent may result in different physiological responses relative to the concentration dose of the agent. Hormesis is characterised by beneficial stimulatory effects exerted at low concentrations, but toxic effects at high concentrations. This biphasic dose-response is a fundamental mechanism of hormesis; a low dose exposure stimulates low levels of stress which the organism is capable of tolerating, and which induces beneficial adaptations as a compensatory response.
The biphasic dose-response is quantitatively demonstrated by a “J-shaped curve”, which illustrates the magnitude of response relative to the concentration dose. Hormesis can be initiated by extrinsic factors, like physical exercise, heat, toxins, or phytochemicals, and intrinsic factors, like energy availability, neurotransmitters, and hormones. The cellular stress induced by the initiating hormetic factor activates adaptive stress response pathways, which protect the cell from more severe stress. Intrinsic initiation of hormesis indicates that it is an integral aspect to normal physiological function, reflecting an evolutionary adaptation to survive harsh environmental conditions.
Hormesis sounds complicated, but you already know of plenty of examples. Take exercise: too little is known to be bad for health, but too much may lead to negative adaptations (overtraining, decreased reproductive hormones, etc). In the middle ground, it takes time to build fitness; the initial stressor must be adapted to, so that initial stressor becomes insufficient – i.e., easier! – over time. In relation to phytochemicals, hormesis provides an explanation for why antioxidant supplement trials largely failed, and in the case of the famous Alpha-Tocopherol, Beta Carotene Cancer Prevention Study, increased risk for cancer. In effect: too much of a good thing is not necessarily a good thing, and hormesis dictates that we only require relatively low concentrations of polyphenol metabolites to benefit from their biological activity.