Hormesis: From Stress to Strength
The aim of this article is to introduce and discuss the idea of “hormesis” and suggest some ways in which an understanding of this concept might be of assistance in the pursuit of health. I stumbled across this term by chance and have since found myself victim of the frequency illusion, whereby hormesis seems to be everywhere I look. This piece is not meant to be hard science but rather an exploration of an idea that has stimulated my thoughts since I first become aware of it. Hormesis is the term given to describe biological systems which benefit from exposure to small doses of toxins or stressors that would otherwise be harmful in larger doses. It was first observed in 1854 and the concept is enjoying somewhat of a renaissance in the field of anti-aging at the moment[1,2]. It describes a dose-response curve where there is no benefit below a certain level of exposure, a range of exposures which lead to benefits (the “hermetic range”), and higher exposures becomes harmful.
An example would be the adaptive response to exercise. The act of exercising is damaging and stressful to the body while you are doing it. Provided the exposure to this stress is not too low or high (i.e. within the hermetic range), this harm will stimulate anti-inflammatory, anti-hypoxic, muscle restoration and other pathways within the body. In response to these harms, the systems of the body not only become better prepared to handle similar stresses in the future, but are also able to handle increased doses of stress. However, if the dose of exercise is greater than the hermetic range, exercise would be harmful and result in injury or inappropriate levels of oxidative stress.
If viewed as hormesis, stress and harm caused by exercise are the key drivers in making the body resilient and robust. This has some interesting implications for exercise performance as well as health in general. Exercise may not necessarily be beneficial per se, and there may be little health benefit in doing “comfortable” exercise which does not stress the body. Potentially, there is an entire range of non-exercise activities that cause harm and stress such that a positive adaptive response is activated within the body. These stresses may be as valid a way to improve “fitness” as exercise-induced stress. Similarly, interventions aimed at countering the harms of training (i.e. reducing inflammation) may actually be counter-productive. For example, while it is generally assumed that ice-baths reduce inflammation, it seems more likely (to me) that this is a non-exercise stress which can stimulate a beneficial adaptive response.
Perhaps the hermetic model helps explain the surprising effectiveness of high-intensity exercise. If the health benefits of exercise stem from the harm and challenge to homeostasis, then pushing beyond your comfort zone is what really matters, even if it is just for a few minutes. This line of reasoning helps explain how 300 minutes of moderate-intensity exercise a week can be less effective than just 20 minutes of high-intensity exercise a week, as was found in the classic Tabata study. Even the most highly trained athletes can be extended well beyond their comfort zone in 4 minutes of activity designed to target their weaknesses.
Exercise is just one of many ways in which stresses are provided to the body. Nutrition is a less intrinsic example, as it is generally understood in very black and white terms which foods are either healthy or unhealthy. However, what if the health advantages of some foods are due to the adaptive response to harmful compounds in the food? This seems particularly plausible for dark leafy greens, wholegrains, and superfoods, which all contain a variety of “noxious” compounds and anti-nutrients. Eaten in the hermetic range, these foods introduce a stress to the body which stimulates an adaptive response. However, at higher doses, the foods can become harmful as such exposure overpowers the body’s ability to recover. Similarly, the health benefits of fasting and intermittent fasting have been linked to this adaptive response to stress[6,7].
In fact, healthiness may simply be a product of successful adaptation to appropriate doses of harms and stresses. Healthy behaviours provide these exposures: sun; cold/heat; fasting; phytonutrients; and exercise. Conversely, ill health and sickness may derive from over or underexposure to these and other stresses. Even things like highly refined foods and air pollution probably have a beneficial hermetic range. However, city-dwelling modern humans are most likely exposed to these and the many other harms of modern civilisation in doses well above the hermetic range.
As mentioned above, this article is an exploration of ideas and even if hormesis is the major driving factor behind health and exercise performance, the exact doses of harms and the full scope of the systems affected in the body are unknown. Hopefully you have found this article stimulating and can see some value in hormesis to enhance your understanding biological systems.
Henschler D. The origin of hormesis: historical background and driving forces. Hum Exp Toxicol. 2006;25(7):347-351.
Calabrese EJ, Mattson MP. How does hormesis impact biology, toxicology, and medicine? NPJ Aging Mech Dis. 2017;3:13.
Milanovic Z, Sporis G, Weston M. Effectiveness of High-Intensity Interval Training (HIT) and Continuous Endurance Training for VO2max Improvements: A Systematic Review and Meta-Analysis of Controlled Trials. Sports Med. 2015;45(10):1469-1481.
Tabata I, Nishimura K, Kouzaki M, et al. Effects of moderate-intensity endurance and high-intensity intermittent training on anaerobic capacity and VO2max. Med Sci Sports Exerc. 1996;28(10):1327-1330.
Son TG, Camandola S, Mattson MP. Hormetic Dietary Phytochemicals. Neuromolecular medicine. 2008;10(4):236-246.
Horne BD, Muhlestein JB, Anderson JL. Health effects of intermittent fasting: hormesis or harm? A systematic review. Am J Clin Nutr. 2015;102(2):464-470.
Lettieri Barbato D, Tatulli G, Aquilano K, Ciriolo MR. Mitochondrial Hormesis links nutrient restriction to improved metabolism in fat cell. Aging (Albany NY). 2015;7(10):869-881.