Hormesis is a concept borrowed from toxicology that explains why certain things that are toxic in high quantities can be beneficial at low doses.
What is hormesis?
Hormesis is a term that comes from toxicology and refers to the paradoxical beneficial effect experienced by an organism exposed to a low dose of a substance or environmental factor which is toxic at higher doses (1). This is called “biphasic dose response” in scientific lingo, often described as U-shaped or J-shape curve (1, 2, 3).
It is believed that the role of hormesis is to restore homeostasis, i.e. a balanced state, when it has been disrupted. This allows organisms to adapt to environmental hazards, evolve and survive (1, 2, 3, 4).
The alternative hypothesis on how hormesis works is that there are two types of receptor for certain substances, which would lead to opposite effects. The first type of receptors would have high affinity for the substance and be present in small quantities, which would explain why low doses of the substance would be enough to trigger a response. The second type of receptors would have a low affinity for the substance and be present in larger quantities, explaining why high doses of the substance would be needed to trigger a response, which would theoretically produce the opposite effect (2).
Besides toxicology, hormesis is now a concept applied in general to biology. Hormetic agents are anything that elicit a positive adaptive response at a low dose. This includes:
Commonly known hormetic agents include exercise (1, 2) and dietary energy (i.e. calorie) restriction and intermittent fasting (1, 2, 4, 5).
Energy restriction has been shown in many animal, insect and other organism models to extend longevity, prevent cancer and age-related cognitive and psychomotor decline. Observational human studies have found associations between energy restriction and reduced morbidity and mortality. This includes a reduction in risk of Alzheimer’s disease, Parkinson’s disease, stroke and atherosclerosis. In addition, caloric restriction may enhance several longevity-supporting mechanisms such as DNA repair, protein synthesis and degradation, immune function, attenuation of oxidative damage and glucose metabolism (2).
On the other hand, energy restriction does not produce a hormetic response in some body cells such as motor neurons in the spinal cord and processes such as wound healing and reproduction (5).
Similarly, alternate day intermittent fasting (i.e. not eating every other day) has been shown in animals to be more effective than caloric restriction in promoting anti-ageing and longevity (2).
For more on longevity and energy restriction check out the posts below:
- Book review: The Longevity Diet (Prof Valter Longo)
- Book review: Eat Like The Animals (Dr David Raubenheimer and Dr Stephen J Simpson)
- Book review: Lifespan (David Sinclair)
- Book review: The Fast 800 (Dr Michael Mosley)
- The 16:8 diet
Vitamins and minerals
Several vitamins (A, D, E, K, B6) and minerals (sodium, potassium, calcium, magnesium, phosphate, chloride, iron, iodine, fluorine, selenium and copper) are regarded as hormetic agents because low intakes can lead to deficiency and high intakes can lead to toxicity (2).
Light to moderate alcohol intake has been associated with a reduced risk of dementia, diabetes, osteoporosis, cardiovascular disease and mortality. On the flip side, excessive alcohol can be detrimental to health by harming multiple body systems (2).
Other stressors that can produce hormetic responses include exposure to temperature extremes (heat and cold), exposure to UV, gamma and X-ray radiation, heavy metals and pro-oxidants. Exposure to these stressors trigger the action of stress response proteins which are responsible for protecting our cells from damage. Perhaps the most well-known proteins within this category are the heat shock proteins (2).
Pesticides and herbicides
Some pesticides and herbicides that can be carcinogenic at high doses may actually have the opposite effect (i.e. protect against cancer) at small doses. These pesticides are readily consumed in the food supply at levels that normally do not cause any harm (2).
Phytochemicals are natural toxins in plants that serve as defence against pathogens, insects and animals (4), and can induce a positive hormetic response when ingested (2, 4). These include:
- isothiocyanates including sulforaphane from broccoli (2, 4, 5) and phenethyl isothiocyanate from turnips, watercress, radishes, etc., which can protect against cancer (4)
- quercetin from red grape seeds which can help reduce oxidative stress (2, 4)
- curcumin from turmeric which can help reduce oxidative stress (3, 4, 5)
- allicin from garlic and onions which can induce Nrf2, a transcription factor that regulates genes that protect cells (5)
- resveratrol from red grapes and red wine, which has antioxidant properties (4, 5) and may improve glucose metabolism (4)
- ferulic acid from tomatoes, sweet corn and rice, which may have anti-inflammatory properties(4)
- luteolin from carrots, fennel, capsicum and fennel, which may prevent certain types of cancer and protect neuronal cells against oxidative damage (4)
- carnosic acid from rosemary which can induce Nrf2 (4)
Phytochemicals are regarded as hormetic agents because the amount we ingest through diet is not high enough to support a benefit from antioxidant activity alone (5). For example, curcumin has very low bioavailability due its poor solubility in water, chemical instability, poor absorption and quick metabolism and excretion. Despite this, it seems to elicit anti-inflammatory, antioxidant, antimicrobial properties, as well as help prevent or combat cancer and atherosclerosis. On the flip side, curcumin can have toxic effects when combined with certain drugs (3).
Summary and recommendations
Hormesis is a process by which an agent that would normally be toxic produces a positive adaptive response when present at a low dose. Examples include exercise, energy (caloric) restriction, heat and cold exposure, phytochemicals from fruits and vegetables, and alcohol. Some hormetic agents can have different effects in different cells and the hormetic response may vary between individuals. However, the bulk of the evidence seems to indicate that eating a diet rich in plant foods and a little alcohol (akin to the Mediterranean diet), getting moderate exercise and introducing occasional dietary energy restriction, intermittent fasting and exposure to extreme cold and/or heat can be beneficial for health and longevity.
- Mattson MP. Hormesis defined. Ageing research reviews. 2007/12/29 ed. 2008 Jan;7(1):1–7.
- Hayes DP. Nutritional hormesis. European journal of clinical `. 2006/08/04 ed. 2007 Feb;61(2):147–59.
- Concetta Scuto M, Mancuso C, Tomasello B, Laura Ontario M, Cavallaro A, Frasca F, et al. Curcumin, Hormesis and the Nervous System. Nutrients. 2019/10/30 ed. 2019 Oct 10;11(10).
- Martucci M, Ostan R, Biondi F, Bellavista E, Fabbri C, Bertarelli C, et al. Mediterranean diet and inflammaging within the hormesis paradigm. Nutrition reviews. 2017/06/09 ed. 2017 Jun 1;75(6):442–55.
- Mattson MP. Dietary factors, hormesis and health. Ageing research reviews. 2007/10/05 ed. 2008 Jan;7(1):43–8.
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