Refers to a biological phenomenon whereby a beneficial effect that can result from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses.
Biphasic dose–effect and time–effect relationships are prevalent for many environmental and endocrine factors.
A low dose of a chemical agent may trigger from an organism the opposite response to a very high dose.
Hormesis is any process in a cell or organism that exhibits a biphasic response to exposure to increasing amounts of a substance or condition.
Within the hormetic zone, there is generally a favorable biological response to low exposures to toxins and other stressors.
Patients with low levels of physical activity are at risk for high levels of oxidative stress, as are individuals engaged in highly intensive exercise programs.
Individuals engaged in moderately intensive, regular exercise experience lower levels of oxidative stress.
High levels of oxidative stress have been linked by some with the increased incidence of a variety of diseases.
This characterizes positive effects at an intermediate dose of a stressor is indicative of hormesis.
The oxidative stress associated with intensive exercise may have long-term health benefits.
Oxidative stress, itself, provides an example of hormesis, but physical exercise does not.
Alcohol is believed to be hormetic in preventing heart disease and stroke,although the benefits of light drinking may have been exaggerated.
As light alcohol consumption increases cancer risk, it does not have a hormetic zone from the point of view of cancer.
Evidence shows that repetitive mild stress exposure has anti-aging effects, and exercise is an example of hormesis in this respect.
Some other molecules, such as celastrols from medicinal herbs and curcumin from the spice turmeric have also been found to have hormetic beneficial effects.
Mitochondria generate most of the cell’s supply of adenosine triphosphate (ATP), a source of chemical energy.
Reactive oxygen species (ROS) are regarded as unwanted by-products of oxidative phosphorylation in mitochondria.
It is proposed that substances which inactivate ROS, such as antioxidants, would lead to a reduction of oxidative stress and thereby produce an increase in lifespan.
ROS may perform lifespan-promoting role as redox signaling molecules which transduce signals from the mitochondrial compartment to other compartments of the cell.
Increased formation of ROS within the mitochondria may produce increased stress resistance and a long-term reduction of oxidative stress.
The reverse effect of the response to ROS stress is named mitochondrial hormesis
Mitochondrial hormesis is hypothesized to be responsible for lifespan-extending and health-promoting capabilities of glucose restriction and physical exercise.
Hormesis has been observed in a number in humans exposed to chronic low doses of ionizing radiation.
A-bomb survivors exposed to high doses of radiation exhibited shortened lifespan and increased cancer mortality.
Individuals exposed to but low-dose radiation has ratios of cancer deaths in A-bomb survivors smaller than those of Japanese averages.
In Taiwan recycled radiocontaminated steel was inadvertently used in the construction of over 100 apartment buildings causing the long-term exposure of 10,000 people.
The average dose rate was 50 mSv/year and a subset of the population received a total dose of over 4,000 mSv over ten years.
The expected cancer deaths in this population would have been 302 with 70 caused by the extra ionizing radiation with the remainder caused by natural background radiation.
The observed cancer rate was quite low at 7 cancer deaths when 232 would be predicted had they not been exposed to the radiation from the building materials.
It is suggested more than 600 substances show a U-shaped dose–response relationship.
Low dose effects of drugs may be different from higher levels.
Intermittent exposure can have opposite effects as continuous exposure of drugs.
Similarly to drug effect, early-life stresses can increase resilience and lack of stress can lead to vulnerability.
The nervous, endocrine, and immune systems are highly adaptive and responsive to stress.
The paradoxical beneficial effects of low-dose stressors, effect relationships for any situation.
Intermittent or pulsatile exposure can generate opposite effects for chronic illness compared with continuous exposure.
The initial exposure can provoke 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 required for healthy growth or homeostasis, which exemplifies how an illness is the doorway to health.
Such benefits include improved health, growth or longevity.
Compounds exhibiting hormetic effects include trace metals, alcohol and caffeine which may be essential or healthful at low doses, but detrimental or toxic at high doses.
Radiation at low exposure associated with reduced rates of cancer and death in industrial workers who handle low-level radioactive materials, in residents of high altitude regions, people exposed to higher levels of natural radon gas; and survivors of atomic blasts a who lived outside of the immediate blast areas.
Dioxin is beneficial at very low doses, but workers exposed to low or moderate levels of dioxin had reduced incidence of many types of cancer.
Dioxin binds to DNA suggesting it can both induce and inhibit carcinogenesis.
Other biological stresses have hormetic effects including calorie restriction, cold temperature, heat shock, and hypergravity.
Hormetic effect also appears to involve several independent physiological systems, including the endocrine and immune systems, tissue repair and growth mechanisms, and neural plasticity.
It is proposed that hormetic stresses work by inducing cellular adaptations brought on by activation of an “anti-stress” gene regulatory network, which in turn activate a cascade of homeostatic pathways which protect cells from stressful environments.
An example is the activation of so-called “heat shock proteins” expressed as an adaptive response to heat stress, allowing the cell to resist heat denaturation of cellular proteins.
Growth of immune cells in response to antigen exposure represents a hormetic adaptation, and the dose of the antigen is critical.
Allergen immunotherapy introduces low doses of an allergen and gradually increasing the dosage to build up tolerance.
Progressive hormesis occurs with weight-training, such that muscular strength can be significantly increased.