Are you feeling comfortable? – Measuring clinical hormesis

Hormesis is a biological phenomenon where exposure to a low dose of a stressor or toxin induces a beneficial adaptive response, whereas higher doses may have detrimental effects. The concept of hormesis is being increasingly appreciated not only in toxicology and in pharmacology, but also in nutrition, clinical medicine, and in situations involving everyday life. Hormesis is an adaptive response of cells and organisms to a moderate and intermittent stressful stimulation. Following such stimulation, the organism must respond, and it has to make a choice: either treat it as a positive ‘challenge’, adapting to it and increasing its robustness, or treat it as a negative ‘threat’ with detrimental consequences for physiology and health. In clinical and everyday situations it is usually difficult to advise patients on how to determine the strength of such stimulation, and when to decide that each new stimulation is too low (ineffective), moderate (appropriate for health), or excessive (damaging to health). In this paper we argue that it is possible to rely on the subjective feelings of ‘comfort vs discomfort’, for deciding about the strength of the stimulus: if each exposure to a stimulation is felt by the individual as a ’comfortable’ event, then it is likely that its effects are beneficial (a hormetic challenge). If it is felt as an ‘uncomfortable’ event, then it is likely that it is damaging to health (a threat). These feelings take place in the anterior insula which evaluates the state of resources for responding to an external or internal event, and are a result of the integration of signals from the amygdala, hippocampus, and the prefrontal cortex. Digital cognitive stimulation and nutritional hormesis are mentioned as two detailed examples.