“What does not kill me, makes me stronger.” – Friedrich Nietzsche
It has been 134 years since the German philosopher wrote those words in his book Twilight of the Idols. Recent scientific findings echo Nietzsche’s sentiments. According to the process of hormesis, certain toxins and physiological stressors can make you stronger when administered at non-lethal doses. This hormetic effect may explain the benefits of many common health practices associated with exercise, diet and lifestyle. Physical exercise offers a particularly striking example of hormesis. The easily observable and measurable stressor of physical exertion leads to greater resilience against disease, aging and psychological and emotional disruption.
The Definition of Hormesis
Hormesis describes a situation in which a substance that is harmful to an organism in large quantities provides beneficial effects to the organism when the quantity of the substance is small. The first observation of this hormetic effect occurred with radiation. Scientists have long known that radiation exposure can lead to cancer. But recent research has shown that extremely low doses of radiation can stimulate DNA repair and delay cancer in mice. Some human epidemiological data even shows that low-dose radiation may reduce the risk of developing cancer.
Dioxins offer another example of the hormetic effect. These environmental pollutants are produced by industrial processes like smelting and the manufacture of some herbicides and pesticides, as well as by natural processes like volcanic eruptions and forest fires. At sufficient levels of exposure, dioxins are highly toxic and may cause cancer and reproductive and developmental problems, damage the immune system and interfere with hormones. However, animals fed low doses of dioxins actually developed fewer liver tumors than those with no dioxin exposure.
Among more common examples, alcohol is toxic at high doses but may help humans live longer when consumed in small amounts. And physical exercise stresses cells and generates free radicals, which can be very damaging. But small, regular doses of physical exertion allow the body to adapt and develop a more efficient defense system. Researchers have also found that hormesis is responsible for many of the health benefits associated with intermittent fasting, cold or heat exposure, high-intensity interval training, altitude training and certain phytonutrients consumed in edible plants.
Hormesis and Oxidative Stress
As mentioned above, hormetic stressors generate low levels of free radicals in our bodies. These free radicals are unstable molecules that react easily with other molecules in the body. Left unchecked, they can wreak havoc on the cells of the body, even damaging a cell’s DNA. An excess of free radicals leads to oxidative stress, which includes cell death, aging and disease.
Fortunately, the human body can use substances called antioxidants to stymie free radicals. Antioxidants are another class of unstable molecules, but unlike free radicals, they don’t typically react with stable molecules. Instead, they react with free radicals to produce two stable molecules and prevent oxidative stress.
In addition to antioxidants, the human body has several defense mechanisms in place to combat free radicals. In the presence of some free radicals, the mitochondria, or energy-producing parts of our cells, generate more copies of themselves. Losing mitochondria is a common hallmark of aging and can cause fatigue due to insufficient cellular fueling. So stimulating mitochondrial growth can provide your cells with more energy and stave off some effects of aging.
The low levels of oxidative stress generated by hormesis also influence a variety of cellular signaling pathways. For example, the presence of free radicals prevents the deterioration of the transcription factor NRF2, a protein that binds to DNA to activate genes that control antioxidant production. More NRF2 means more antioxidants and other detoxification enzymes. And these compounds make the body more efficient at neutralizing toxins and high levels of oxidative stress. In other words, triggering a little bit of oxidative stress trains the body to handle more oxidative stress in the future.
Effects on the Body
These mechanisms allow the body to use hormetic oxidative stress to promote stress resilience, repair cellular damage and DNA, reduce inflammation, support the elimination of toxins, improve blood sugar regulation and reduce the risk of cancer. In fact, some scientists now believe that exposing oneself to hormetic stress is essential to achieve optimal health. According to Dr. Elissa Epel, director of the University of California San Francisco Aging, Metabolism and Emotion Center, “biologically, the lack of acute stressors prevents the intermittent episodes of cellular ‘housecleaning’ activities that slow aging.” So introducing small, acute stressors allows for cellular housekeeping and slows aging.
Additionally, increasing evidence shows that resilience acquired through one hormetic stressor may help the body adapt to other stressors. This hormetic cross-adaptation even applies to psychological stressors like depression and anxiety. In other words, introducing little challenges in one part of your life can improve your mental health and resilience.
Back to Nietzsche
Contrary to the Nietzsche aphorism that opened this article, there are limits to the benefits of hormesis. Exposing yourself to radiation levels just below what would kill you won’t make you stronger, just very sick. And while seriously injuring yourself during a workout might allow you to develop psychological resilience as you rehab, you could also build resilience without the physical debilitation.
We can think of hormesis as a U-shaped curve, with the amount of a stressor on the x-axis and the degree of adverse health risk on the y-axis. Too little exercise leads to a higher risk of adverse health outcomes, just like extremes of exercise. And while consuming plant phytochemicals can promote overall health, avoiding those foods or consuming high doses of concentrated phytochemicals can be unhealthy.
Hormesis, Exercise and Crossover
Instead, hormetic benefits come from pushing your limits slightly. Go a little longer without eating, hold your breath for a few seconds beyond discomfort, get a bit colder or hotter than feels comfortable, push yourself a little harder on your last interval or lift, and your body will adapt to this new stimulus and make you more resilient in the future.
In fact, basic exercise physiology has long embraced a variant of the hormetic effect. For example, strength training works by damaging muscle cells. In response, the muscles repair the damage and increase their size and strength in the process. And exercise offers a very tangible way to embrace hormesis and gain some non-physical benefits. Compared to exposing oneself to radiation or other toxins, exercise is low risk. It’s also easy to measure—increasing the dose is as simple and trackable as adding more weight to a barbell or running an interval a little faster.
Furthermore, the crossover effect of hormesis provides another explanation for the non-physical benefits of exercise. Safe, easily observable physical activity promotes harder-to-see outcomes like reducing depression and anxiety, repairing DNA and cellular damage, combating oxidative stress, reducing inflammation, eliminating toxins, improving blood sugar regulation and reducing the risk of cancer.
The Hormetic Effect in KineSophy
I have long argued for the non-physical benefits of regular physical movement. Hormesis offers another biological explanation for these benefits. We observe that tackling physical challenges leads to improvements in physical fitness and greater psychological resilience that transcends the gym or playing field. Hormesis shows us how these physical stressors act on the body to promote overall wellness.