Hormesis in Health and Chronic Diseases

'What doesn't kill you makes you stronger'. Hormesis, the paradoxical beneficial effects of low-dose stressors, can be better defined as the biphasic dose-effect or time-effect relationship for any substance. Here we review hormesis-like phenomena in the context of chronic diseases for many substances, including lifestyle factors and endocrine factors. Intermittent or pulsatile exposure can generate opposite effects compared with continuous exposure. An initial exposure can elicit an adaptive stress response with long-lasting protection against subsequent exposures. Early-life stress can increase resilience in later life and lack of stress can lead to vulnerability. Many stressors are naturally occurring and are required for healthy growth or homeostasis, which exemplifies how 'illness is the doorway to health'.